Hydrochloric Acid → 1-[2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl]piperidin-4-yl)-4,5-dimethylphenyl]propan-1-one

A saturated solution of hydrogen chloride in EtOAc (10 mL) was added to a solution of 85 (1.15 g, 3.33 mmol) in DCM (5.0 mL) at ambient temperature. After 30 min the volatiles were evaporated in vacuo. The above residue was resuspended in DCM (10 mL) and to this stirred solution was added DIEA (1.73 mL, 9.9 mmol), (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid 80 (1.06 g, 3.3 mmol), and HATU (1.39 g, 3.6 mmol). After approximately 18 h, the reaction mixture was poured into water and extracted three times with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), filtered, and the filtrate concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0%-20% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent) afforded 86 as a colorless oil.

1. customAfter 30 min the volatiles were evaporated in vacuo
2. extractionextracted three times with EtOAc
3. washThe combined organic extracts were washed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationthe filtrate concentrated in vacuo
7. customPurification of the crude residue by flash chromatography on silica gel (
8. washgradient elution
9. addition0%-20% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent)

ORDレコード

ord-cd4812bccbf2466d96ab81caa9833df2

出典データセット

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07419990B2