Triethylamine → Methyl (3S,4R)-4-(4-chlorophenyl)pyrrolidine-3-carboxylate hydrochloride

To a solution of methyl (3S,4R)-1-benzyl-4-(4-chlorophenyl)pyrrolidine-3-carboxylate, from preparation 25 (0.93 g, 2.8 mmol) in dichloromethane (9 mL) cooled with an ice-bath was added 1-chloroethyl chloroformate (0.46 mL). The reaction mixture was allowed to warm to room temperature and stirred for 48 hours. The reaction mixture was then cooled to 0° C. and triethylamine (0.43 mL, 3.1 mmol) was added followed by additional 1-chloroethylchloroformate (0.31 mL, 2.8 mmol). The ice-bath was removed and the reaction mixture was stirred at room temperature for 1.5 hours before being diluted with dichloromethane, washed with water (20 mL), 5% aqueous citric acid (20 mL) and then dried over magnesium sulfate and filtered. The solvent was removed in vacuo and the residual oil was refluxed in methanol (20 mL) for 1 hour. The solvent was then removed in vacuo and the residue was triturated with diethyl ether and filtered to give the desired product as a white solid, 0.874 g.

1. temperaturecooled with an ice-bath
2. temperatureThe reaction mixture was then cooled to 0° C.
3. customThe ice-bath was removed
4. stirringthe reaction mixture was stirred at room temperature for 1.5 hours
5. additionbefore being diluted with dichloromethane
6. washwashed with water (20 mL), 5% aqueous citric acid (20 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. customThe solvent was removed in vacuo
10. temperaturethe residual oil was refluxed in methanol (20 mL) for 1 hour
11. customThe solvent was then removed in vacuo
12. customthe residue was triturated with diethyl ether
13. filtrationfiltered

ORD record

ord-bc7e2fd3dca14c6ca224b30e7eea221f

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07649002B2