Dichloromethane → 1-tert-Butyl 2-methyl (2S,4R)-4-((methanesulfonyl)oxy)pyrrolidine-1,2-dicarboxylate

Temperature

2.5 °C

In a 1.0 L 4-necked RB flask fitted with a mechanical stirrer and a reflux condenser and under a nitrogen blanket, 1-tert-butyl(2S,4R) 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (100 gm) and dichloromethane (1000 ml) were added at a temperature 25-35° C. while stirring. The reaction mixture was cooled to 0-5° C. and triethyl amine (18.2 g, 0.180M) was added. The reaction temperature was maintained for 15 min and then methane sulfonyl chloride (16.6 g, 0.145M) was added dropwise at 0-5° C. while stirring. The reaction mixture was maintained for 3-4 hr at 0-5° C. The reaction was monitored by TLC. After ascertaining the completion of the reaction, water (168 ml) was added while stirring and the layers were separated. One more dichloromethane (600 ml) extraction was given to aqueous layer. Two water washings were given to the MDC layer. The dichloromethane layer was dried over anhydrous sodium sulphate. The MDC layer (95%) was concentrated under vacuum below 45° C. After distillation n-hexane (600 ml) was added and the mixture stirred for 20 min at 0-5° C. The solid precipitate was filtered and the product was washed with hexane (200 ml). The product was dried at 40-45° C. under vacuum.

1. additionwere added at a temperature 25-35° C.
2. temperatureThe reaction temperature was maintained for 15 min
3. stirringwhile stirring
4. temperatureThe reaction mixture was maintained for 3-4 hr at 0-5° C
5. additionwas added
6. stirringwhile stirring
7. customthe layers were separated
8. extractionOne more dichloromethane (600 ml) extraction
9. dry with materialThe dichloromethane layer was dried over anhydrous sodium sulphate
10. concentrationThe MDC layer (95%) was concentrated under vacuum below 45° C
11. distillationAfter distillation n-hexane (600 ml)
12. additionwas added
13. stirringthe mixture stirred for 20 min at 0-5° C
14. filtrationThe solid precipitate was filtered
15. washthe product was washed with hexane (200 ml)
16. customThe product was dried at 40-45° C. under vacuum

ORD record

ord-8b0ce1a077e14b6f9c618e5308000e89

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893103B2