β-Nitroacrylates as Useful Building Blocks for the Synthesis of Alkyl Indole-2-Carboxylates

Abstract

Polyfunctionalized alkyl indole 2-carboxylates can be easily synthesized starting form β-nitroacrylates and o-bromoanilines through an addition–elimination process followed by an intramolecular palladium-catalyzed Heck reaction.

Key words

indoles - Heck reaction - β-nitroacrylates - cyclization - Michael addition

Over the years, several synthetic methods have been proposed that can be used to access functionalized indole systems.[1] This continuous interest reflects the importance of this heterocyclic system due to its presence in numerous synthetic and naturally occurring molecules.[2] The main synthetic tactics used for preparing functionalized indoles can be classified as: (i) construction of a pyrrole system onto a benzene precursor,[3] (ii) benzannulation of pyrroles,[4] and (iii) derivatization of a preformed indole core, usually by C-3 Friedel–Crafts reaction in combination with electron-poor alkenes (a),[5] or by the functionalization of the benzylic position via alkylideneindolenine intermediates (b)[6] (Scheme [1]).

In this context, pathway (i) has been the most investigated and, recently, efforts have been directed towards metal-catalyzed ring construction, which ensures mild reaction conditions and the possibility of introducing a variety of functionalities into the indole ring.[7] Although some important goals have been reached, further drawbacks need to be overcome, and the identification of new substrates that can be easily converted into functionalized indoles remains a research topic of great interest.

In this regard, following our ongoing studies on β-nitro­acrylate chemistry,[8] we have disclosed a novel and simple one-pot synthesis of α-enamino esters 4 that can be directly transformed into alkyl indole-2-carboxylates 5 by ­palladium-catalyzed Heck reaction (Scheme [2]).[9]

Scheme 1 Common synthetic approaches for the synthesis of functionalized indoles

Scheme 2 Our synthetic approach

The thus-obtained indole derivatives 5, or their acid form (R² = H), belong to an important sub-class of indoles that are widely used as strategic intermediates for the synthesis of important biologically active molecules,[10] however, despite their importance, only a few synthetic methods have been reported. Among them, the Japp–Klingemann reaction followed by Fischer rearrangement (A),[11] and the Hemetsberger–Knittel indole synthesis (B) (Scheme [3])[12] are two of the most well-known methods; however, both these approaches have important limitations. The former approach is rather complex, requiring the preparation of the appropriate β-keto esters and the arendiazonium salts, and harsh acidic reaction conditions are needed to promote the Fischer cyclization. On the other hand, the Hemetsberger–Knittel synthesis entails the use of hazardous azidoacetates, restricting functionalization to the benzene ring and usually furnishing the indoles in very low yields.

Scheme 3 Japp–Klingemann/Fischer (A) and Hemetsberger–Knittel (B) approaches

In this regard, our synthetic strategy, which exploits the high reactivity of β-nitroacrylates 1 in combination with o-bromoanilines 2, represents a novel, convenient and alternative strategic approach.

To optimize our protocol, we first studied the aza-Michael reaction and were pleased to observe complete conversion of 1a and 2a into 3a at 70 °C (24 h), under solvent-free conditions (Table [1]). We then treated crude 3a with a range of bases and solvents, obtaining the best yield of 4a (87%) by using two equivalents of TBD on polymer[13] in MeCN (Table [1], entry 3).

Table 1 Optimization Studies

Entry	Base (equiv)	Solvent	Time (h)	Yield of 4a (%)a
1	TBD on polymer (1)	MeCN	9	41
2	TBD on polymer (1.5)	MeCN	9	67
3	TBD on polymer (2)	MeCN	5	87
4	KF/Al2O3 (2)	MeCN	5	31
5	carbonate on polymer (2)	MeCN	5	43
6	TMG (2)	MeCN	3	77
7	TBD on polymer (2)	CPME	5	–
8	TBD on polymer (2)	CH2Cl2	5	81
9	TBD on polymer (2)	EtOAc	5	9

^a Yield of pure isolated product.

Having optimized the synthesis of 4a, we extended our protocol to prepare title compounds 5a–j by submitting crude 4a–j, which were readily obtained by TBD-filtration and solvent evaporation, to the Kondo reaction conditions,[9a] obtaining, in all cases, good overall yields of indoles (Table [2]).

Table 2 Preparation of Indole-2-carboxylic Acid Esters 5

Indole 5		Yield (%)a
5a		60 (52)b
5b		56
5c		50
5d		44
5e		59
5f		51
5g		55
5h		51
5i		49
5j		47

^a Yield of pure isolated product.

^b Heck reaction conditions: Microwave, 190 °C, MeCN, 1.5 h.

In conclusion, our approach provides simple access to functionalized alkyl indole-2-carboxylates, which are useful synthetic intermediates.[14] By the appropriate selection of β-nitroacrylate and o-bromoaniline precursors, it is possible to introduce different substituents onto the benzene ring, modify the ester moiety, and introduce several functionalities onto the C-3 alkyl chain. Furthermore, thanks to the simple conditions used to prepare intermediates 4, the whole process involves just one aqueous work-up and a single chromatographic purification.

Acknowledgment

The authors thank the Universities of Camerino and Parma and MIUR-Italy (FIRB National Project ‘Metodologie di nuova generazione nella formazione di legami carbonio-carbonio e carbonio-­eteroatomo in condizioni eco-sostenibili’) for financial support.

• References and Notes

• 1a Gribble GW. Contemp. Org. Synth. 1994; 145
• 1b Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000; 1045
• 1c Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
• 2a Faulkner DJ. Nat. Prod. Rep. 2002; 19: 1
• 2b Saxton JE In The Alkaloids . Cordell GA. Academic Press; New York: 1998
• 2c Sundberg RJ In Indoles . Academic Press; New York: 1997
• 2d Saxton JE. Nat. Prod. Rep. 1997; 14: 559
• 3a Robinson B In The Fischer Indole Synthesis . Wiley-Interscience; New York: 1982
• 3b Dalpozzo R, Bartoli G. Curr. Org. Chem. 2005; 9: 163
• 3c Thyagarajan BS, Hillard JB, Reddy KV, Majumdar KC. Tetrahedron Lett. 1974; 1999
• 3d Baudin J.-B, Comménil M.-G, Julia SA, Lorne R, Mauclaire L. Bull. Soc. Chim. Fr. 1996; 133: 329
• 3e Houlihan WJ, Parrino VA, Uike Y. J. Org. Chem. 1981; 46: 4511
• 3f Gassman PG, Gruetzmacher G, Van Bergen TJ. J. Am. Chem. Soc. 1973; 95: 6508
• 4a Palmieri A, Gabrielli S, Lanari D, Vaccaro L, Ballini R. Adv. Synth. Catal. 2011; 353: 1425
• 4b Hosmane RS, Hiremath SP, Schneller SW. J. Chem. Soc., Perkin Trans. 1 1973; 2450
• 4c Andrews JF. P, Jackson PM, Moody CJ. Tetrahedron 1993; 49: 7353
• 4d Barluenga J, Vazquez-Villa H, Ballestreros A, Gonzalez JM. Adv. Synth. Catal. 2005; 347: 526
• 4e Attanasi OA, Favi G, Filippone P, Lillini S, Mantellini F, Spinelli D, Stenta M. Adv. Synth. Catal. 2007; 349: 907
• 4f Muratake H, Natsume M. Heterocycles 1990; 31: 683
• 4g Katritzky AR, Ledoux S, Nair SK. J. Org. Chem. 2003; 68: 5728
• 5a Ballini R, Clemente RR, Palmieri A, Petrini M. Adv. Synth. Catal. 2006; 348: 191
• 5b Bartoli G, Bosco M, Giuli S, Giuliani A, Lucarelli L, Marcantoni E, Sambri L, Torregiani E. J. Org. Chem. 2005; 70: 1941
• 5c Bandini M, Melloni A, Tommasi S, Umani-Ronchi A. Synlett 2005; 1199
• 5d Bandini M, Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
• 6 Palmieri A, Petrini M, Shaikh RR. Org. Biomol. Chem. 2010; 8: 1259
• 7a Larock RC, Yum EK, Refvik MD. J. Org. Chem. 1998; 63: 7652
• 7b Nazaré M, Schneider C, Lindenschmidt A, Will DW. Angew. Chem. Int. Ed. 2004; 43: 4526
• 7c Arcadi A, Bianchi G, Marinelli F. Synthesis 2004; 610
• 7d Kothandaraman P, Mothe SR, Toh SS. M, Chan PW. H. J. Org. Chem. 2011; 76: 7633
• 7e Nanjo T, Tsukano C, Takemoto Y. Org. Lett. 2012; 14: 4270
• 8a Ballini R, Gabrielli S, Palmieri A. Curr. Org. Chem. 2010; 14: 65
• 8b Ballini R, Gabrielli S, Palmieri A. Synlett 2010; 2468
• 8c Palmieri A, Gabrielli S, Ballini R. Adv. Synth. Catal. 2010; 352: 1485
• 8d Palmieri A, Gabrielli S, Cimarelli C, Ballini R. Green Chem. 2011; 13: 3333
• 8e Gabrielli S, Palmieri A, Panmand DS, Lanari D, Vaccaro L, Ballini R. Tetrahedron 2012; 68: 8231
• 8f Gabrielli S, Ballini R, Palmieri A. Monatsh. Chem. 2013; 144: 509
• 8g Palmieri A, Gabrielli S, Ballini R. Green Chem. 2013; 15: 2344
• 9a Yamazaki K, Kondo Y. Chem. Commun. 2002; 210
• 9b Yamazaki K, Nakamura Y, Kondo Y. J. Org. Chem. 2003; 68: 6011
• 10a Rosauer KG, Ogawa AK, Willoughby CA, Ellsworth KP, Geissler WM, Myers RW, Deng Q, Chapman KT, Harris G, Moller DE. Bioorg. Med. Chem. Lett. 2003; 13: 4385
• 10b Parrish JP, Kastrinsky DB, Stauffer F, Hedrick MP, Hwang I, Boger DL. Bioorg. Med. Chem. 2003; 11: 3815
• 10c Boger DL, Boyce CW. J. Org. Chem. 2000; 65: 4088
• 10d Dai Y, Guo Y, Guo J, Pease LJ, Li J, Marcotte PA, Glaser KB, Tapang P, Albert DH, Richardson PL, Davidsen SK, Michaelides MR. Bioorg. Med. Chem. 2003; 13: 1897
• 11a Japp FR, Klingemann F. Ber. Dtsch. Chem. Ges. 1887; 20: 2942
• 11b Delfourne E, Roubin C, Bastide J. J. Org. Chem. 2000; 65: 5476
• 11c Meyer MD, Kruse LI. J. Org. Chem. 1984; 49: 3195
• 12a Knittel D. Synthesis 1985; 186
• 12b Hemetsberger H, Knittel D. Monatsh. Chem. 1972; 103: 194
• 12c Venable JD, Cai H, Chai W, Dvorak CA, Grice CA, Jablonowski JA, Shah CR, Kwok AK, Ly KS, Pio B, Wei J, Desai PJ, Jiang W, Nguyen S, Ling P, Wilson SJ, Dunford PJ, Thurmond RL, Lovenberg TW, Karlsson L, Carruthers NI, Edwards JP. J. Med. Chem. 2005; 48: 8289
• 13 The 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) bound to polystyrene (3 mmol/g) was purchased from Sigma–Aldrich (01961-5G-F) and used directly without any manipulation.
• 14 Synthesis of Indoles 5; General Procedure: o-Bromoaniline 1 (0.5 mmol) and β-nitroacrylate 2 (0.5 mmol) were stirred at 70 °C for 24 h, then MeCN (3 mL) and TBD (1 mmol, 333 mg) were added and the resulting solution was stirred at r.t. for 5 h. Finally, after TBD filtration (washing with EtOAc) and solvent evaporation, the crude material 4 was dissolved in DMF (4 mL), treated with Pd₂(dba)₃ (32 mg, 0.034 mmol), P(o-Tol)₃ (42 mg, 0.138 mmol), Et₃N (0.96 mL, 6.9 mmol), and heated at 110 °C for 12 h. After cooling, the reaction was quenched with 2 M HCl (10 mL), extracted with Et₂O (3 × 30 mL) and the organic extracts were dried over Na₂SO₄. After filtration and solvent evaporation at reduced pressure, the crude indole 5 was purified by flash chromatography (hexane–EtOAc). Ethyl 3-Ethyl-1H-indole-2-carboxylate (5a): White solid; mp 91–93 °C. IR (Nujol): 747, 1257, 1673, 3329 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.29 (t, J = 7.7 Hz, 3 H), 1.44 (t, J = 7.3 Hz, 3 H), 3.14 (q, J = 7.7 Hz, 2 H), 4.43 (q, J = 7.3 Hz, 2 H), 7.14 (t, J = 7.7 Hz, 1 H), 7.32 (t, J = 8.1 Hz, 1 H), 7.38 (d, J = 7.7 Hz, 1 H), 7.70 (d, J = 8.1 Hz, 1 H), 8.78 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.7, 15.7, 18.3, 60.9, 111.9, 120.1, 121.0, 123.0, 125.7, 127.1, 127.9, 136.2, 162.7. MS (EI, 70 eV): m/z (%) = 217 (100) [M]⁺, 202, 188, 171, 170, 156, 143, 128, 115, 101, 89, 77, 63, 51, 39, 29. Anal. Calcd for C₁₃H₁₅NO₂ (217.26): C, 71.87; H, 6.96; N, 6.45. Found: C, 71.91; H, 7.00; N, 6.41. Ethyl 3-Methyl-1H-indole-2-carboxylate (5b): Pale-orange solid; mp 128–130 °C. IR (Nujol): 744, 780, 1257, 1683, 3326 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.45 (t, J = 7.3 Hz, 3 H), 2.63 (s, 3 H), 4.44 (q, J = 7.3 Hz, 2 H), 7.08–7.44 (m, 3 H), 7.68 (d, J = 8.1 Hz, 1 H), 8.73 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 10.1, 14.7, 60.9, 111.8, 120.1, 120.4, 121.0, 123.6, 125.8, 128.8, 136.0, 162.9. MS (EI, 70 eV): m/z (%) = 203 [M]⁺, 174, 157 (100), 129, 102, 77, 51, 29. Anal. Calcd for C₁₂H₁₃NO₂ (203.24): C, 70.92; H, 6.45; N, 6.89. Found: C, 70.98; H, 6.48; N, 6.86. Propyl 3-Methyl-1H-indole-2-carboxylate (5c): Pale-yellow solid; mp 102–105 °C. IR (Nujol): 744, 780, 1242, 1682, 3328 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.06 (t, J = 7.3 Hz, 3 H), 1.77–1.89 (m, 2 H), 2.62 (s, 3 H), 4.33 (t, J = 6.8 Hz, 2 H), 7.14 (t, J = 7.3 Hz, 1 H), 7.29–7.40 (m, 2 H), 7.67 (d, J = 8.1 Hz, 1 H), 8.70 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 10.2, 10.9, 22.4, 66.6, 111.8, 120.1, 120.3, 121.0, 123.7, 125.8, 128.8, 136.1, 163.1. MS (EI, 70 eV): m/z (%) = 217 [M]⁺, 174, 157 (100), 129, 102, 77, 51, 41, 29. Anal. Calcd for C₁₃H₁₅NO₂ (217.26): C, 71.87; H, 6.96; N, 6.45. Found: C, 71.84; H, 6.93; N, 6.47. Methyl 3-Nonyl-1H-indole-2-carboxylate (5d): White solid; mp 65–67 °C. IR (Nujol): 749, 1250, 1675, 3326 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.07–1.43 (m, 12 H), 1.62–1.73 (m, 2 H), 3.06–3.14 (m, 2 H), 3.95 (s, 3 H), 7.11–7.16 (m, 1 H), 7.28–7.40 (m, 2 H), 7.69 (dd, J = 0.9, 9.0 Hz, 1 H), 8.75 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.4, 22.9, 24.9, 29.6, 29.8, 29.9, 30.0, 31.3, 32.2, 51.9, 111.9, 120.1, 121.2, 123.0, 125.8, 126.0, 128.2, 136.2, 163.1. MS (EI, 70 eV): m/z (%) = 301 [M]⁺, 242, 188 (100), 156, 128. Anal. Calcd for C₁₉H₂₇NO₂ (301.42): C, 75.71; H, 9.03; N, 4.65. Found: C, 75.74; H, 9.05; N, 4.64. Ethyl 3-(4-Cyanobutyl)-1H-indole-2-carboxylate (5e): White solid; mp 115–117 °C. IR (Nujol): 752, 1021, 1250, 1697, 2248, 3374 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.44 (t, J = 7.3 Hz, 3 H), 1.67–1.78 (m, 2 H), 1.81–1.92 (m, 2 H), 2.36 (t, J = 6.8 Hz, 2 H), 3.17 (t, J = 7.3 Hz, 2 H), 4.43 (q, J = 7.3 Hz, 2 H), 7.12–7.18 (m, 1 H), 7.29–7.42 (m, 2 H), 7.66 (d, J = 8.1 Hz, 1 H), 8.81 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.7, 17.3, 23.9, 25.3, 29.9, 61.1, 112.1, 120.0, 120.5, 120.8, 123.5, 124.0, 125.9, 128.0, 136.1, 162.4. MS (EI, 70 eV): m/z (%) = 270 [M]⁺, 224, 202, 197, 156 (100), 128, 101, 77, 29. Anal. Calcd for C₁₆H₁₈N₂O₂ (270.33): C, 71.09; H, 6.71; N, 10.36. Found: C, 71.06; H, 6.70; N, 10.40. Cyclopentyl 3-Ethyl-5-methyl-1H-indole-2-carboxylate (5f): White solid; mp 113–115 °C. IR (Nujol): 783, 799, 1255, 1679, 3314 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.26 (t, J = 7.7 Hz, 3 H), 1.58–2.06 (m, 8 H), 2.45 (s, 3 H), 3.06 (q, J = 7.7 Hz, 2 H), 5.44–5.50 (m, 1 H), 7.14 (dd, J = 1.3, 8.5 Hz, 1 H), 7.24–7.28 (m, 1 H), 7.45 (s, 1 H), 8.61 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 15.8, 18.4, 21.8, 24.0, 33.2, 77.8, 111.6, 120.2, 123.5, 126.1, 127.6, 128.1, 129.4, 134.5, 162.7. MS (EI, 70 eV): m/z = 271 [M]⁺, 203, 188, 186, 185 (100), 170, 142, 115, 41 Anal Calcd. for C₁₇H₂₁NO₂ (271.35): C, 75.25; H, 7.80; N, 5.16. Found: C, 75.29; H, 7.82; N, 5.13. Ethyl 5-Methyl-3-phenethyl-1H-indole-2-carboxylate (5g): White solid; mp 132–134 °C. IR (Nujol): 755, 779, 798, 1601, 1678, 3309 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.44 (t, J = 7.3 Hz, 3 H), 2.47 (s, 3 H), 2.91–2.99 (m, 2 H), 3.34–3.41 (m, 2 H), 4.41 (q, J = 7.3 Hz, 2 H), 7.13–7.33 (m, 7 H), 7.41 (s, 1 H), 8.75 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.8, 21.8, 27.4, 37.6, 60.9, 111.7, 120.2, 123.6, 123.8, 126.1, 127.7, 128.2, 128.5, 128.8, 129.6, 134.5, 142.6, 162.7. MS (EI, 70 eV): m/z (%) = 307 [M]⁺, 216 (100), 170, 142, 115, 91, 65, 39, 29. Anal. Calcd for C₂₀H₂₁NO₂ (307.39): C, 78.15; H, 6.89; N, 4.56. Found: C, 78.19; H, 6.91; N, 4.53. Ethyl 5-Methoxy-3-[(2-phenyl-1,3-dioxolan-2-yl)methyl]-1H-indole-2-carboxylate (5h): White solid; mp 144–146 °C. IR (Nujol): 752, 762, 779, 1022, 1258, 1539, 1668, 3326 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.37 (t, J = 7.3 Hz, 3 H), 3.68–3.85 (m, 9 H), 4.27 (q, J = 7.3 Hz, 2 H), 6.96 (dd, J = 2.5, 8.5 Hz, 1 H), 7.11 (d, J = 2.5 Hz, 1 H), 7.22–7.30 (m, 4 H), 7.36–7.42 (m, 2 H), 8.72 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.6, 36.5, 55.9, 60.8, 64.9, 102.9, 110.7, 112.4, 117.0, 117.7, 125.8, 126.2, 127.9, 129.5, 131.2, 142.9, 154.4, 162.5. MS (EI, 70 eV): m/z (%) = 381 [M]⁺, 232, 186, 149 (100), 105, 77. Anal. Calcd for C₂₂H₂₃NO₅ (381.42): C, 69.28; H, 6.08; N, 3.67. Found: C, 69.32; H, 6.10; N, 3.66. Ethyl 3-(3-Acetoxypropyl)-5-methoxy-1H-indole-2-carboxylate (5i): Pale-yellow solid; mp 74–76 °C. IR (Nujol): 782, 1220, 1674, 1732, 3327 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.42 (t, J = 7.3 Hz, 3 H), 1.97–2.07 (m, 2 H), 2.05 (s, 3 H), 3.11–3.18 (m, 2 H), 3.87 (s, 3 H), 4.12 (t, J = 6.8 Hz, 2 H), 4.41 (q, J = 7.3 Hz, 2 H), 6.97–7.04 (m, 2 H), 7.27 (d, J = 8.5 Hz, 1 H), 8.73 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.7, 21.3, 21.4, 29.7, 56.0, 61.0, 64.5, 101.0, 113.0, 117.3, 123.2, 124.1, 128.4, 131.4, 154.6, 162.4, 171.4. MS (EI, 70 eV): m/z (%) = 319 [M]⁺, 259, 231, 213, 186 (100), 158, 115, 43. Anal. Calcd for C₁₇H₂₁NO₅ (319.35): C, 63.94; H, 6.63; N, 4.39. Found: C, 63.98; H, 6.65; N, 4.37. Ethyl 6-Methoxy-3-pentyl-1H-indole-2-carboxylate (5j): White solid; mp 108–110 °C. IR (Nujol): 781, 1247, 1671, 3311 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 0.89 (t, J = 6.8 Hz, 3 H), 1.33–1.39 (m, 4 H), 1.41 (t, J = 7.3 Hz, 3 H), 1.61–1.71 (m, 2 H), 3.02–3.07 (m, 2 H), 3.85 (s, 3 H), 4.40 (q, J = 7.3 Hz, 2 H), 6.76–6.82 (m, 2 H), 7.52–7.55 (m, 1 H), 8.61 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.3, 14.7, 22.8, 25.0, 31.0, 32.2, 55.7, 60.6, 93.7, 111.5, 122.0, 122.2, 122.8, 126.3, 137.1, 159.2, 162.2. MS (EI, 70 eV): m/z (%) = 289 [M]⁺, 243, 232, 216, 204, 186 (100), 160, 158, 115, 89, 41, 29. Anal. Calcd for C₁₇H₂₃NO₃ (289.37): C, 70.56; H, 8.01; N, 4.84. Found: C, 70.60; H, 8.00; N, 4.82.