N,N-Dimethylglycine → 3-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenoxy]benzoic acid

HRID 1799204ノート

反応式

HRID 1799204 の反応式
Br[C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:13][NH:12][C:11](=[O:14])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[OH:15][C:16]1[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=1)[C:19]([O:21]C)=[O:20].CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.[Cu]I>[O:14]=[C:11]1[NH:12][CH2:13][C@@H:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([CH:3]=2)[O:15][C:16]2[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=2)[C:19]([OH:21])=[O:20])[CH2:10]1

参加物

8

反応物 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 88068Methyl 3-HydroxybenzoateHCID 66724952(4R)-4-(3-bromo-4-chlorophenyl)pyrrolidin-2-one

生成物 1

HCID 667248973-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenoxy]benzoic acid

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a mixture of (4R)-4-(3-bromo-4-chlorophenyl)pyrrolidin-2-one (0.1 g, 0.36 mmol) and methyl 3-hydroxybenzoate (0.055 g, 0.36 mmol) in dioxane (1 mL) was added N,N-dimethylglycine (0.011 g, 0.11 mmol), copper(I) iodide (0.02 g, 0.11 mmol) and cesium carbonate (0.23 g, 0.72 mmol). The mixture was stirred overnight at 100° C. The mixture was then diluted with ethyl acetate (50 mL), washed with a 10% aq. HCl solution then brine, and concentrated to give 3-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenoxy]benzoic acid, which was treated with HCl as described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride to provide the title compound (22). MS (ESI) m/z 350.07 (M+H)+.

後処理

  1. washwashed with a 10% aq. HCl solution
  2. concentrationbrine, and concentrated

出典と根拠

ORDレコード
ord-dd1d577506f341b5ab40c63f381000d3
出典データセット
uspto-grants-2013_01
特許番号
US08344028B2

反応ノート

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