Methanol → HCID 131720894, compound

Participants

Reaction Steps

Combine 3-(4-fluorophenyl)-3-(2-hydroxyethyl)pyrrolidine (32 mmol) and butanone (400 mL). Add a solution of (R,R)-di-p-anisoyltartaric acid (32 mmol) in butanone (80 mL). Heat to reflux. After 15 minutes, cool to ambient temperature and evaporate in vacuo to give a residue. Combine the residue and butanone (1000 mL) and methanol (430 mL) and heat. Add methanol (about 100 mL). Slowly cool to ambient temperature to give a solid. After 18 hours, filter the solid. Recrystallize the solid from butanone/methanol (80 mL/80 mL) to give (−)-3-(4-fluorophenyl)-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt. [α]2D0=−98.9 (c=0.70, methanol). Analysis on HPLC, on an analytical sample of the 3,4,5-trimethoxybenzamide derivative, using a CHIRALPAK AD 25 cm×0.46 cm column eluting with pentane/ethanol/methanol/triethylamine (80/15/10/0.1) with a flow rate of 1.0 mL/minute indicates an enantiomeric excess of 99.6%, (99.6% ee), the 3,4,5-trimethoxybenzamide prepared from (−)-3-(4-fluorophenyl)-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt gave a retention time of 23.0 minutes, the 3,4,5-trimethoxybenzamide prepared from (+)-3-(4-fluorophenyl)-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt gave a retention time of 15.4 minutes.

Provenance & Evidence