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

HRID 1930220노트

반응식

HRID 1930220 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-bromo-6-fluoro-2H-isoquinolin-1-one (312) 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 is achieved. For the isolation procedure, the solvent is removed i. vac., the residue was taken up in saturated sodium bicarbonate solution and extracted three times with dichloromethane. The organic layers are dried with MgSO4 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, which gave additional 2.62 g of the desired product. Rt=1.71 min (Method C). Detected mass: 362.3/364.3 (M+H+).

후처리

  1. customFor the isolation procedure, the solvent is removed i
  2. extractionextracted three times with dichloromethane
  3. dry with materialThe organic layers are dried with MgSO4
  4. customevaporated

출처 및 근거

ORD 기록
ord-9252e381d3d9484398dfa154c63d36c0
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188117B2

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