Synlett 2019; 30(10): 1183-1186
DOI: 10.1055/s-0037-1611774
cluster
© Georg Thieme Verlag Stuttgart · New York

Efficient Flow Electrochemical Alkoxylation of Pyrrolidine-1-carbaldehyde

Nasser Amri
a  School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK   Email: wirth@cf.ac.uk
,
Ryan A. Skilton
b  Vapourtec Ltd., 21 Park Farm Business Centre, Bury St Edmunds, IP28 6TS, UK
,
Duncan Guthrie
b  Vapourtec Ltd., 21 Park Farm Business Centre, Bury St Edmunds, IP28 6TS, UK
,
a  School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK   Email: wirth@cf.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 31 January 2019

Accepted after revision: 11 February 2019

Publication Date:
26 March 2019 (eFirst)

Published as part of the Cluster Electrochemical Synthesis and Catalysis

Abstract

We report on the optimization of the alkoxylation of pyrrolidine-1-carbaldehyde by using a new electrochemical microreactor. Precise control of the reaction conditions permits the synthesis of either mono- or dialkoxylated reaction products in high yields.

Supporting Information

 
  • References and Notes

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  • 15 2-Methoxypyrrolidine-1-carbaldehyde (2); Typical ProcedureA 0.1 M solution of aldehyde 1 in MeOH (60 mL) containing Et4NBF4 (0.05 M) was sonicated to ensure complete dissolution of the reactant, then pumped through one microreactor at 0.5 mL/min by using a syringe pump or the Vapourtec E series, while a constant current of 640 mA was applied. The first 5 mL were discarded, and the remaining reaction mixture was collected for 110 min (55 mL). MeOH was removed under reduced pressure, and the crude product was washed with H2O (50 mL), to remove the supporting electrolyte, then extracted with CH2Cl2 (3 × 30 mL). The organic layers were combined, dried (MgSO4), filtered, evaporated, and dried under high vacuum. The residue was purified by chromatography [silica gel, hexane–EtOAc (1:1)] to give a colorless oil; yield: 629 mg (89%). The NMR spectra showed the presence of a ~5:1 mixture of rotamers.1H NMR (400 MHz, CDCl3): δ (major) = 8.40 (s, 1 H), 4.92 (d, J = 4.8 Hz, 1 H), 3.58−3.40 (m, 2 H), 3.26 (s, 3 H), 2.13−1.79 (m, 4 H); δ (minor) = 8.29 (s, 1 H), 5.37 (d, J = 4.8 Hz, 1 H), 3.58−3.40 (m, 2 H), 3.38 (s, 3 H), 2.13−1.79 (m, 4 H). 13C NMR (101 MHz, CDCl3): δ (major) = 161.4, 89.7, 54.4, 42.7, 31.8, 21.4; δ (minor) = 162.6, 85.5, 56.6, 45.2, 31.9, 22.1.