Sodium hydride → 7-bromo-6-fluoro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one

HRID 1913123노트

반응식

HRID 1913123 반응식
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][C:3]=1[F:13].[H-].[Na+].[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1>CC(N(C)C)=O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([CH2:22][C:21]3[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=3)[C:9]2=[O:12])=[CH:4][C:3]=1[F:13]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 598182537-Bromo-6-fluoro-1,2-dihydroisoquinolin-1-one

생성물 1

HCID 598182577-bromo-6-fluoro-2-(4-methoxybenzyl)isoquinolin-1(2H)-one수율 116.3%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매2회

실험 절차

9.66 g (39.9 mmol) of 7-Bbromo-6-fluoro-2H-isoquinolin-1-one (95) were dissolved in 180 ml of dimethyl acetamide and 1.92 g (48.0 mmol) of sodium hydride (60%) were added. After 1 h at room temperature a solution of 7.50 g (48.0 mmol) of 4-methoxy benzylchloride in 25 ml of dimethyl acetamide was added. The mixture was stirred at room temperature until complete conversion was achieved. The solvent was removed under reduced pressure, the residue was taken up in saturated sodium bicarbonate solution and extracted three times with dichloromethane. The organic layers were dried with magnesium sulfate and evaporated to yield 16.8 g of a dark oil as crude product, which was stirred in methanol. Filtration of the precipitate gave 6.56 g of the title compound as a yellow solid. The mother liquor was evaporated and the residue purified by preparative HPLC to yield additional 2.62 g of the desired product. Rt=1.71 min (Method C). Detected mass: 362.3/364.3 (M+H+).

후처리

  1. customThe solvent was removed under reduced pressure
  2. extractionextracted three times with dichloromethane
  3. dry with materialThe organic layers were dried with magnesium sulfate
  4. customevaporated

출처 및 근거

ORD 기록
ord-3946d9c3b6e64458b4193941bfbdb2d4
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609691B2

반응 노트

불러오는 중…