Dimethyl Sulfoxide → (3R,4S)-3-formyl-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Temperature

-78 °C

Oxalyl chloride (3.3 mL, 2M in CH2Cl2, 6.42 mmol) was stirred in dichloromethane (3 mL) in a three-necked flask. The reaction mixture was cooled to −78° C., and dimethyl sulfoxide (0.91 mL, 12.85 mmol) was added so that the internal temperature did not exceed −65° C. The reaction mixture was then stirred for 15 minutes. The (3R,4S)-3-hydroxymethyl-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester (713 mg, 2.57 mmol) in dichloromethane (6 mL) was added dropwise keeping the internal temperature below −65° C. and then stirred for 15 minutes. Diisopropylethylamine (4.5 mL, 25.7 mmol) was added keeping the internal temperature below −65° C. and then stirred for 20 minutes. The cooling bath was removed and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated to give a colorless oil, which was purified by flash silica gel chromatography eluting with ethyl acetate: hexanes (1:4) to give 496 mg (70%) of (3R,4S)-3-formyl-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester.

1. customdid not exceed −65° C
2. customthe internal temperature below −65° C.
3. stirringstirred for 15 minutes
4. customthe internal temperature below −65° C.
5. stirringstirred for 20 minutes
6. customThe cooling bath was removed
7. stirringthe reaction mixture was stirred at room temperature for 2 h
8. concentrationThe reaction mixture was concentrated
9. customto give a colorless oil, which
10. customwas purified by flash silica gel chromatography
11. washeluting with ethyl acetate: hexanes (1:4)

ORD record

ord-42d92c086c31462fbfad98f984555691

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08076349B2