849706-05-4

Upstream product

• 93102-05-7 N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine 
• 320385-10-2 (E)-3-benzyloxypropenoyl-(2'S)-bornane-10,2-sultam 
• 21286-54-4 D-camphor-10-sulfonyl chloride 
• 72597-34-3 (+/-)-10-Camphorsulfonamide 
• 107869-45-4 (+)-(camphorylsulfonyl)imine 
• 100-46-9 benzylamine 
• 53215-95-5 N-(trimethylsilylmethyl)benzylamine 
• 108448-77-7 (+)-camphorsultam 
• 127762-22-5 (E)-3-(benzyloxy)acrylic acid 
• 154581-21-2 (E)-3-benzyloxypropenoyl chloride 
• 35963-20-3 (R)-10-camphorsulfonic acid 

Relevant academic research and scientific papers

Process for the preparation of substituted pyrrolidine derivatives and intermediates

Two syntheses are provided; one for the preparation of (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol, and other for the preparation of (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol. (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol is prepared using the achiral ylide prepared from benzylamine instead of phenethylamine (Scheme 3) which provides a crystalline intermediate. The synthesis of (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol is achieved from (S)-diethylmalate as described in Scheme 4. A process for preparing camphor sultam is also provided.

A practical large-scale synthesis of (3R,4R)-4-(Hydroxymethyl)pyrrolidin-3- ol via asymmetric 1,3-dipolar cycloaddition

(3R,4R)-4-(Hydroxymethyl)pyrrolidin-3-ol (1), which is a useful intermediate for the synthesis of various bioactive molecules, has been synthesized in 51% overall yield by 1,3-dipolar cycloaddition reaction from the dipolarophile, (E)-3-benzyloxypropenoyl-(2′S)-bornane-10,2-sultam (5), and the achiral ylide precursor, N-(benzyl)-N-(methoxymethyl)-N- (trimethylsilylmethyl)amine (6), without using chromatography and the subsequent reduction with LAH and catalytic hydrogenation. The diastereomers 7 and 8 were separated by crystallization, and efficient procedures were developed for the subsequent reactions to afford 1.