ホームMCPワークベンチSkills
ホームワークベンチ通知マイページ
llms.txt · MCPガイドプライバシーポリシー · 利用規約 · サポートv1.8.0
  1. ホーム
  2. /反応

Oxalyl chloride → 4-(Chlorocarbonyl)-3-fluorophenyl acetate

HRID 418830
ノート
印刷プレビュー

反応式

HRID 418830 の反応式
[F:1][C:2]1[CH:10]=[C:9]([O:11][C:12](=[O:14])[CH3:13])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(Cl)(=O)C([Cl:18])=O>ClCCl.CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([O:11][C:12](=[O:14])[CH3:13])[CH:8]=[CH:7][C:3]=1[C:4]([Cl:18])=[O:5]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 65578Oxalyl chlorideHCID 227214164-Acetoxy-2-fluorobenzoic acid

生成物 1

HCID 227436454-(Chlorocarbonyl)-3-fluorophenyl acetate収率 101.8%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 2-fluoro-4-hydroxybenzoic acid (1.87 g, 12 mmol) in 30 mL pyridine was added acetic anhydride (1.84 g, 18 mmol) and catalytic amount of DMAP and the reaction mixture was stirred at rt for 15 h. The pyridine was removed under reduced pressure; the residue was dissolved in EtOAc (100 mL), washed with 1N HCl (20 mL), water (20 mL) and dried over anhydrous Na2SO4. Removal of solvent gave 2-fluoro-4-acetoxybenzoic acid in 57% yield (1.35 g). To a suspension of 2-fluoro-4-acetoxybenzoic acid (1.33 g, 6.71 mmol) in 10 mL anhydrous dichloromethane was added oxalyl chloride (2.56 g, 20.13 mmol). Two drops of DMF was added and the reaction mixture was stirred at rt for 3 h. The solvent and excess oxalyl chloride were removed under reduced pressure to give 1.48 g of 2-fluoro-4-acetoxybenzoyl chloride which was used in next step without purification. To a solution of 2′-hydroxyacetophenone (0.93 g, 6.83 mmol) in 15 mL anhydrous pyridine was added 2-fluoro-4-acetoxybenzoyl chloride (1.48 g, 6.83 mmol) and the reaction mixture was stirred at rt for 15 h under nitrogen atmosphere. Then the reaction mixture was poured into 100 mL 2N HCl, extracted with EtOAc (200 mL). The crude compound was purified by column chromatography (Silica Gel 230-400 mesh; 20% EtOAc in hexanes as eluent) to give 4-acetoxy-2-fluorobenzoic acid 2-acetyl phenyl ester (1.14 g, 53%). The ester compound (0.74 g, 2.34 mmol) was dissolved in 10 mL anhydrous THF. Potassium tert-butoxide (0.53 g, 4.68 mmol) was added in portions and stirred at rt under nitrogen for 1 h. A yellow solid was formed. The reaction mixture was quenched with 15 mL saturated aqueous ammonium chloride. EtOAc (100 mL) was added and the organic phase was separated and dried over anhydrous Na2SO4. Removal of solvent gave crude product (0.725 g) which was used in next step without further purification. This crude compound (0.72 g, 2.62 mmol) was dissolved in 10 mL glacial AcOH, conc. HCl (1 mL) was added and the reaction mixture was stirred at 110° C. for 4 h. The reaction mixture was cooled to rt. The solid was isolated by filtration, washed with AcOH and dried under vacuum to give 126 mg (21%) over 2 steps. MS (ES) m/z: 256.89 (M), 255.86 (M−1); Mp. 287-289° C.

後処理

  1. customThe solvent and excess oxalyl chloride were removed under reduced pressure

出典と根拠

ORDレコード
ord-b2f91ef2367d40748ddab9e140d4f4f8
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093273B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート