반응 #58006

반응 방정식

hydrogen chloride

111

tert-butyl 4-[2-((1S)-1-{[(benzyloxy)carbonyl]amino}propyl)-4,5-dimethylphenyl]piperidine-1-carboxylate

DIEA

(3S,4R)-1-tert-butyl4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid

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

HATU

→

112

benzyl {(1S)-1-[2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}piperidin-4-yl)-4,5-dimethylphenyl]propyl}carbamate

용매

water

EtOAc

DCM

반응 조건

후처리

1. 1
   기타After 30 min the volatiles were evaporated in vacuo
2. 2
   추출extracted three times with DCM
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%-10% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent)

실험 절차

A saturated solution of hydrogen chloride in EtOAc (10.0 mL) was added to a solution of 111 (830 mg, 1.7 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 (10.0 mL) and to this stirred solution was added DIEA (886 μL, 5.1 mmol), (3S,4R)-1-tert-butyl4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid 80 (542 mg, 1.7 mmol), and HATU (710 mg, 1.87 mmol). After approximately 18 h, the reaction mixture was poured into water and extracted three times with DCM. 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%-10% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent) afforded 112 as a colorless oil.

출처