Dimethyl Sulfoxide → (S)-3-(1-Carbamoyl-1,1-diphenylmethyl)-1-(7-oxohept-1-yl)pyrrolidine

To a stirred solution of (S)-3-(1-carbamoyl-1,1-diphenylmethyl)-1-(7-hydroxyhept-1-yl)pyrrolidine (31.00 g, 78.57 mmol); N,N-diisopropylethylamine (68.4 mL, 392.8 mmol); and methyl sulfoxide (60.7 mL, 785.7 mmol) in dichloromethane (780 mL) under an atmosphere of nitrogen at −15° C., was added sulfur trioxide pyridine complex (37.5 g, 235.71 mmol) portion-wise over a 40 min. period. The reaction mixture was maintained between −10° C. and −20° C. during the addition. The reaction was then stirred in this temperature range for 40±10 min. Deionized water (300 mL) was added and the mixture was stirred for 10 minutes. The organic layer was separated and washed with deionized water (200 mL), followed by saturated aqueous sodium chloride (200 mL) and the organic layer was then dried with magnesium sulfate (10 g). The magnesium sulfate was filtered off and washed with dichloromethane (50 mL) and the solvent was reduced in vacuo. The resultant syrup was washed with petroleum ether (2×200 mL) to remove the remaining pyridine and DMSO and the resulting white solid was dried in vacuo to give 33.02 g of the title intermediate (98% yield; >93% purity by chiral HPLC Method A).

1. temperatureThe reaction mixture was maintained between −10° C. and −20° C. during the addition
2. stirringthe mixture was stirred for 10 minutes
3. customThe organic layer was separated
4. washwashed with deionized water (200 mL)
5. dry with materialthe organic layer was then dried with magnesium sulfate (10 g)
6. filtrationThe magnesium sulfate was filtered off
7. washwashed with dichloromethane (50 mL)
8. washThe resultant syrup was washed with petroleum ether (2×200 mL)
9. customto remove the remaining pyridine and DMSO
10. customthe resulting white solid was dried in vacuo

ORD record

ord-3216fa197dcd4602a003043949c9b28b

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080565B2