반응 #58004

반응 방정식

hydrogen chloride

85

tert-butyl 4-(4,5-dimethyl-2-propionylphenyl)piperidine-1-carboxylate

DIEA

(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid

(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride salt

HATU

→

86

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

용매

water

EtOAc

DCM

반응 조건

후처리

1. 1
   기타After 30 min the volatiles were evaporated in vacuo
2. 2
   추출extracted three times with EtOAc
3. 3
   세척The combined organic extracts were washed with brine
4. 4
   건조dried (MgSO4)
5. 5
   여과filtered
6. 6
   농축the filtrate concentrated in vacuo
7. 7
   기타Purification of the crude residue by flash chromatography on silica gel (
8. 8
   세척gradient elution
9. 9
   workup.ADDITION0%-20% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent)

실험 절차

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.

출처