Sulfuric Acid → (3R,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidine-3-carboxylic acid methyl ester

HRID 587344Notes

Reaction equation

[CH2:1]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C@@H:10]([C:20]([OH:22])=[O:21])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[C:28](OC)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>CO>[CH3:28][O:21][C:20]([C@@H:10]1[C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)[CH2:12][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9]1)=[O:22]

Participants

Conditions

Temperature: 60 °C

Procedure

To a white suspension of (3R,4R)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidine-3-carboxylic acid (72.31 g, 229 mmol) in methanol (725 mL) was added slowly sulfuric acid (25.8 ml, 457.9 mmol). The resulting dark brown solution was stirred for 19 h at 60° C. After cooling to 0° C., tert-butylmethylether (1.6 L) was added and the solution was set to pH=9 with aqueous sodium carbonate (1M, 480 mL). The aqueous layer was separated and extracted with further tert-butylmethylether (410 mL). The organic layers were washed with brine (310 mL) and dried over sodium sulfate. Concentration afforded the title compound (74.18 g, 98%) as a light brown oil. MS m/e: 330.3/332.3 [M+H]+.

Workup

temperatureAfter cooling to 0° C.
customThe aqueous layer was separated
extractionextracted with further tert-butylmethylether (410 mL)
washThe organic layers were washed with brine (310 mL)
dry with materialdried over sodium sulfate
concentrationConcentration

Sources & evidence

ORD record: ord-f76a34c537094aed9d9a6d3e7152338f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09226916B2

Reaction notes

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