A highly efficient flow reactor process for the synthesis of N-Boc-3,4-dehydro-l-proline methyl ester

The multi-step preparation of N-Boc-3,4-dehydro-l-proline methyl ester using a modular flow reactor is reported. The use of immobilised reagents and scavengers in pre-packed glass tubes allows us to obtain the pure product in 87% overall yield, 97% purity, and >98% enantiomeric excess without any additional purification step. Our flow-based protocol enables the rapid multi-gram synthesis (about 9 g/12 h) of the desired product.

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(2S,4R)-1-tert-Butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylateC11H19NO5[α]D20=-14 (c 1.00 CHCl3)Source of chirality: trans-4-hydroxy-l-prolineAbsolute configuration: (2S,4R)

(S)-tert-Butyl methyl 2H-pyrrole-1,2(5H)-dicarboxylateC11H17NO4Ee >98%[α]D20=-237 (c 1.00 CH3OH)Source of chirality: trans-4-hydroxy-l-prolineAbsolute configuration: (S)