Methyl (2S)-1-methyl-5-oxoprolinate → (5S)-5-(Hydroxymethyl)-1-methyl-2-pyrrolidinone

Temperature

-78 °C

A stirred solution of 0.68 g (4.33 mmole) (S)-Methyl 1-methyl-5-oxopyrrolidine-2-carboxylate in 15 ml dry tetrahydrofuran was cooled to −78° C. and under argon atmosphere, 2.2 ml (2.2 mmole) of 1M lithium aluminum hydride solution in tetrahydrofuran was added drop by drop during 20 minutes, stirred at −78° C. for 1 hour and removing the cooling bath left to warm up to 0° C. at stirring. While ice cooling, 0.22 ml 10% of sodium hydroxide aqueous solution was added, stirred for 10 minutes, then 0.22 ml of water was added and the reaction mixture stirred for 1.5 hours allowing it to warm to room temperature. The precipitate was filtered and washed with 5×2 ml of ethyl acetate. The combined filtrates were dried over magnesium sulfate and evaporated at 35° C. in good vacuum, giving 0.52 g (93%) product which was pure enough for the next step.

1. customremoving the cooling bath
2. waitleft
3. temperatureto warm up to 0° C.
4. stirringat stirring
5. additionWhile ice cooling, 0.22 ml 10% of sodium hydroxide aqueous solution was added
6. stirringstirred for 10 minutes
7. addition0.22 ml of water was added
8. stirringthe reaction mixture stirred for 1.5 hours
9. temperatureto warm to room temperature
10. filtrationThe precipitate was filtered
11. washwashed with 5×2 ml of ethyl acetate
12. dry with materialThe combined filtrates were dried over magnesium sulfate
13. customevaporated at 35° C. in good vacuum

ORD record

ord-a66d95f33d144bf4ba017109b5d87857

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440948B2