Water → 3-[7-Chloro-2-(4-methoxy-benzyl)-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

HRID 1621302노트

반응식

HRID 1621302 반응식
[H-].[Na+].[Cl:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][N:10]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11]2=[O:14])=[CH:6][C:5]=1F.O.[C:26]([O:30][C:31]([N:33]1[CH:38]2[CH2:39][CH2:40][CH:34]1[CH2:35][CH:36]([OH:41])[CH2:37]2)=[O:32])([CH3:29])([CH3:28])[CH3:27]>CC(N(C)C)=O>[C:26]([O:30][C:31]([N:33]1[CH:38]2[CH2:39][CH2:40][CH:34]1[CH2:35][CH:36]([O:41][C:5]1[CH:6]=[C:7]3[C:12](=[CH:13][C:4]=1[Cl:3])[C:11](=[O:14])[N:10]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)[CH:9]=[CH:8]3)[CH2:37]2)=[O:32])([CH3:29])([CH3:27])[CH3:28]

참가 물질

6

반응물 4

HCID 962WaterHCID 24758Sodium hydrideHCID 21187725tert-Butyl 3-hydroxy-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 598182477-Chloro-6-fluoro-2-[(4-methoxyphenyl)methyl]isoquinolin-1(2H)-one

생성물 1

HCID 670228553-[7-Chloro-2-(4-methoxy-benzyl)-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester수율 80.1%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매3회

실험 절차

528 mg of sodium hydride (60%) were suspended in 8 mL of dimethyl acetamide and 1.00 g of 3-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (70), dissolved in 4 mL of dimethyl acetamide, were added dropwise. After 1 h, 1.40 g of 7-Chloro-6-fluoro-2-(4-methoxy-benzyl)-2H-isoquinolin-1-one (62), dissolved in another 8 mL of dimethyl acetamide, were added. The reaction mixture was stirred at room temperature until the reaction was complete. 30 mL of water were added, the resulting suspension extracted three times with a mixture of dichloromethane and 2-propanol (3:1) and the combined organic layers were evaporated. Water was added and the crude product was subjected to lyophilization to remove remainders of dimethyl acetamide. The obtained crude product was purified by silica gel chromatography to yield 1.85 g of the title compound as a mixture of diastereoisomers (71). Rt=1.95 min, 2.03 min (Method C). Detected mass: 525.0 (M+H+).

후처리

  1. additionwere added dropwise
  2. additionwere added
  3. extractionthe resulting suspension extracted three times
  4. additionwith a mixture of dichloromethane and 2-propanol (3:1)
  5. customthe combined organic layers were evaporated
  6. additionWater was added
  7. customto remove remainders of dimethyl acetamide
  8. customThe obtained crude product
  9. customwas purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-bf6d0eddf15b47dfa383d9f3ec55c17f
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772492B2

반응 노트

불러오는 중…