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

HRID 1930220ノート

反応式

HRID 1930220 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒2 回

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-9252e381d3d9484398dfa154c63d36c0
出典データセット
uspto-grants-2012_05
特許番号
US08188117B2

反応ノート

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