Ammonium Chloride → HCID 59548966、化合物

(R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid 2a (0.3 g, 0.54 mmol), 10 mL of dichloromethane and 5 mL of tert-butanol were added into a 100 mL reaction flask, followed by addition of 0.3 mL of triethylamine and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.277 g, 1.09 mmol) under stirring. After stirring at room temperature for 2 hours, 10 mL of tert-butanol and potassium tert-butoxide (0.24 g, 2.16 mmol) were added to the solution. The reaction mixture was stirred at room temperature for another 2 hours and monitored by thin layer chromatography until the disappearance of the starting materials. 10 mL of statured ammonium chloride was added to the reaction mixture and white precipitates were formed. The precipitates were filtered through a pad of 100-200 mesh silica gel and 50 mL of water was added to the filtrate. Then the filtrate was extracted with ethyl acetate (25 mL×5). The combined organic phase was washed with 30 mL of saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (R)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid tert-butyl ester 36a (0.11 g, yield 33.6%) as a white solid.

1. stirringAfter stirring at room temperature for 2 hours
2. stirringThe reaction mixture was stirred at room temperature for another 2 hours
3. customwhite precipitates
4. customwere formed
5. filtrationThe precipitates were filtered through a pad of 100-200 mesh silica gel and 50 mL of water
6. additionwas added to the filtrate
7. extractionThen the filtrate was extracted with ethyl acetate (25 mL×5)
8. washThe combined organic phase was washed with 30 mL of saturated brine
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe resulting residue was purified by silica gel column chromatography

ORDレコード

ord-663ccf69b664485b8d0110529a7a5ebd

出典データセット

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08207161B2