Methanesulfonyl chloride → HCID 86631210, compound

Diisopropylethylamine (0.36 ml, 2.1 mmol) and 0.15 ml (1.9 mmol) of methanesulfonyl chloride were added under ice cooling to a solution of 397 mg (1.4 mmol) of (S)-(4-bromophenyl)(2-(hydroxymethyl)pyrrolidin-1-yl)methanone synthesized in the same manner as in step (i) of Reference Example 8 in methylene chloride (15 ml) solution, and the mixture was stirred for 2 hr. The reaction solution was diluted with 45 ml of ethyl acetate and was washed with a saturated aqueous ammonium chloride solution. The aqueous layer was extracted twice with 5 ml of ethyl acetate. The organic layers were combined and were washed with 25% brine. The organic layer was dried over anhydrous sodium sulfate and was filtered. The filtrate was concentrated under the reduced pressure, and the residue was dissolved in 10 ml of N,N-dimethylformamide. Sodium azide (146 mg, 2.2 mmol) was added to the solution, and the mixture was stirred at 50° C. for 5 hr. The reaction solution was diluted with 20 ml of ethyl acetate, and the diluted solution was washed five times with 10 ml of 12.5% brine. The organic layer was dried over anhydrous sodium sulfate and was filtered, and the filtrate was concentrated under the reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1) to give 194 mg (yield 45%) of the title compound.

1. washwas washed with a saturated aqueous ammonium chloride solution
2. extractionThe aqueous layer was extracted twice with 5 ml of ethyl acetate
3. washwere washed with 25% brine
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. filtrationwas filtered
6. concentrationThe filtrate was concentrated under the reduced pressure
7. dissolutionthe residue was dissolved in 10 ml of N,N-dimethylformamide
8. stirringthe mixture was stirred at 50° C. for 5 hr
9. washthe diluted solution was washed five times with 10 ml of 12.5% brine
10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
11. filtrationwas filtered
12. concentrationthe filtrate was concentrated under the reduced pressure
13. customThe residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1)

ORD record

ord-48018674868f4ee19594a5a15276dae0

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07871982B2