Methanesulfonyl chloride → HCID 89938215, compound

Temperature

2.5 °C

To a stirred solution of 3-hydroxy-4,4-dimethylcyclopent-1-enecarbonitrile (1.5 g, 10.93 mmol) in dichloromethane (20 ml) was added diisopropylethylamine, (5.73 ml, 32.8 mmol) under nitrogen atmosphere. Reaction mixture was cooled to 0-5° C. Methane sulfonyl chloride (1.278 ml, 16.40 mmol) in 2 ml dichloromethane was added drop wise at 0-5° C. in 10 mins. Reaction mixture was stirred at 0-5° C. for 3 h. Progress of reaction was monitored by TLC. Reaction mixture was diluted with dichloromethane (20 ml) and washed with water (2×10 ml), organic layer was dried on sodium sulfate and concentrated under reduced pressure to get sticky compound which was dissolved in dry N,N-dimethylformamide (15 ml) and cooled to 0-5° C. followed by addition of diisopropylethylamine (5.73 ml, 32.8 mmol) and 1-(4-fluorophenyl)piperazine (1.971 g, 10.93 mmol) under nitrogen atmosphere. Reaction mixture was gradually warmed to 25-30° C. and stirring continued for 16 h. Progress of reaction was monitored by TLC. Reaction mixture was concentrated under reduced pressure to obtain crude product which was dissolved in ethyl acetate (100 ml) and washed with water (3×25 ml). Combined organic layer was dried on sodium sulphate and concentrated under reduced pressure to get crude oily product. Crude compound was purified over silica gel (100-200 mesh) by flash column chromatography using 20% ethyl acetate in hexane to obtain title compound (0.260 g).

1. customReaction mixture
2. customReaction mixture
3. customProgress of reaction
4. customReaction mixture
5. washwashed with water (2×10 ml), organic layer
6. customwas dried on sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customto get sticky compound which
9. temperaturecooled to 0-5° C.
10. customReaction mixture
11. temperaturewas gradually warmed to 25-30° C.
12. stirringstirring
13. waitcontinued for 16 h
14. customProgress of reaction
15. customReaction mixture
16. concentrationwas concentrated under reduced pressure
17. customto obtain crude product which
18. washwashed with water (3×25 ml)
19. customCombined organic layer was dried on sodium sulphate
20. concentrationconcentrated under reduced pressure
21. customto get crude oily product
22. customCrude compound was purified over silica gel (100-200 mesh) by flash column chromatography

ORD record

ord-0460e9718d7d43e6888e46cefea1b87b

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359367B2