Ethyl 4-piperidinecarboxylate → 4'-[2-(2-Chloro-4-trifluoromethanesulfonyloxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid ethyl ester

HRID 333827노트

반응식

HRID 333827 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([O:23][S:24]([C:27]([F:30])([F:29])[F:28])(=[O:26])=[O:25])[CH:5]=[CH:6][C:7]=1[CH:8]([CH3:22])[C:9]([C:15]1[CH:20]=[CH:19][N:18]=[C:17](Cl)[CH:16]=1)([OH:14])[C:10]([F:13])([F:12])[F:11].[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1)=[O:35])[CH3:32]>CN1CCCC1=O.O>[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][N:39]([C:17]2[CH:16]=[C:15]([C:9]([OH:14])([C:10]([F:12])([F:11])[F:13])[CH:8]([C:7]3[CH:6]=[CH:5][C:4]([O:23][S:24]([C:27]([F:28])([F:29])[F:30])(=[O:25])=[O:26])=[CH:3][C:2]=3[Cl:1])[CH3:22])[CH:20]=[CH:19][N:18]=2)[CH2:38][CH2:37]1)=[O:35])[CH3:32]

참가 물질

5

반응물 2

HCID 70770Ethyl 4-piperidinecarboxylateHCID 86629107Trifluoro-methanesulfonic acid 3-chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenyl ester

생성물 1

HCID 866291084'-[2-(2-Chloro-4-trifluoromethanesulfonyloxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid ethyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

Trifluoro-methanesulfonic acid 3-chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenyl ester (Example 135-Step 1, 1.0 g) and piperidine-4-carboxylic acid ethyl ester (0.773 mL) in 1-methyl-2-pyrrolidon (10 mL) were heated at 220° C. in a microwave oven for 30 minutes. The reaction mixture was then diluted with water (100 mL), extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (70 g silica gel, heptane/acetic acid isopropylester 80/20 to 70/30) to give the title compound as light yellow viscous oil (119 mg). MS (m/e)=619.2 (MH+).

후처리

  1. customwere heated at 220° C. in a microwave oven for 30 minutes
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (70 g silica gel, heptane/acetic acid isopropylester 80/20 to 70/30)

출처 및 근거

ORD 기록
ord-8db02720d2f8410abcd0b1bdbab74083
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883786B2

반응 노트

불러오는 중…