Dimethyl Sulfoxide → (-)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one

Temperature

0 °C

A cold (−76° C.), stirred solution of oxalyl chloride (0.8 mole) in dichloromethane (1.4 L) was treated with dimethyl sulfoxide (116 mL, 1.64 mole) over 40 minutes while keeping the internal temperature below −60° C. After stirring the solution for 45 minutes, a solution containing (−)-(4R*,5R*)-5-hydroxymethyl-1-methyl-4-phenylpyrrolidin-2-one (150 g, 0.73 mole) in dichloromethane (1L) was added over a 30 minute period (T<−60° C.) and stirring continued for 45 minutes. Hunig's base (diisopropylethylamine, 509 mL, 2.92 mole) was then added dropwise (T<−60° C.), the mixture was stirred for 45 minutes and then quenched with 1N hydrochloric acid solution (cold, 1.5L) while warming to 0° C. The layers were separated and the organic layer was washed twice with hydrochloric acid (700 mL of 2N, then 500 mL of 1N), dried over magnesium sulfate, filtered and concentrated in vacuo to give (−)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one as tan, crystalline solids, 137 g (93%). NMR (CDCl3) 67 2.81 (m, 2, CH2), 2.91 (s,3H, CH3) 4.02 (q, J=9 Hz, 1H, CH), 4.38 (dd, J=9.1, 1.9 Hz), 7.21-7.39 (m, 5H, Ar), 9.17 (d, J=1.9 Hz, 1H, CHO).

1. customthe internal temperature below −60° C
2. additionwas added over a 30 minute period (T<−60° C.)
3. stirringstirring
4. waitcontinued for 45 minutes
5. stirringthe mixture was stirred for 45 minutes
6. customquenched with 1N hydrochloric acid solution (cold, 1.5L)
7. customThe layers were separated
8. washthe organic layer was washed twice with hydrochloric acid (700 mL of 2N
9. dry with material500 mL of 1N), dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-59afddcc7cc845cb812fc3dc732fd05c

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06784167B2