Dimethylformamide → 3-{5-[(1R)-2-Amino-1-(carboxymethyl)ethyl]-2-chlorophenyl}benzoic acid hydrochloride

HRID 1799207

反応式

HRID 1799207 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].C[O:16][C:17]([C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1)=[O:18].CN(C=[O:32])C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[ClH:8].[NH2:12][CH2:13][C@@H:9]([C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([C:23]2[CH:24]=[C:19]([CH:20]=[CH:21][CH:22]=2)[C:17]([OH:18])=[O:16])[CH:3]=1)[CH2:10][C:11]([OH:14])=[O:32]

参加物

8

反応物 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 66724952(4R)-4-(3-bromo-4-chlorophenyl)pyrrolidin-2-one

生成物 1

HCID 667250703-{5-[(1R)-2-Amino-1-(carboxymethyl)ethyl]-2-chlorophenyl}benzoic acid hydrochloride

試薬・触媒・溶媒 3

HCID 74236Tetrabutylammonium Bromide触媒HCID 167845palladium(II) acetate触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

(4R)-4-(3-Bromo-4-chlorophenyl)pyrrolidin-2-one (0.5 g, 0.55 mmol) and 3-methoxycarbonylphenyl boronic acid (0.144 g, 0.55 mmol) were mixed with DMF (2 mL). The mixture was degassed by alternately applying a vacuum and flushing with nitrogen. Palladium acetate (0.025 g, 0.11 mmol) and tetrabutylammonium bromide (0.053 g, 0.165 mmol) were added followed by potassium phosphate (0.35 g, 1.65 mmol). The mixture was stirred overnight at 90° C., then cooled to room temperature, diluted with ethyl acetate (30 mL), washed with a 10% aqueous HCl solution then brine, and concentrated in vacuo. The product, 3-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid, was then 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 (25). 1H-NMR (400 MHz, CD3OD): δ8.03-8.06 m, 2H), 7.65-7.68 (m, 2H), 7.55-7.57 (m, 1H), 7.33-7.37 (m, 2H), 3.42-3.49 (m, 1H), 3.2-3.26 (m, 2H), 2.77-2.83 (dd, J=16.8, 6.4 Hz, 1H), 2.63-2.69 (dd, J=16.4, 7.6 Hz, 1H); MS (ESI) m/z 333.98 (M+H)+.

後処理

  1. customThe mixture was degassed
  2. customflushing with nitrogen
  3. temperaturecooled to room temperature
  4. washwashed with a 10% aqueous HCl solution
  5. concentrationbrine, and concentrated in vacuo
  6. additionThe product, 3-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid, was then treated with HCl
  7. customas described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride

出典と根拠

ORDレコード
ord-a8c954e7ca1545b491053e4d53ea3417
出典データセット
uspto-grants-2013_01
特許番号
US08344028B2

関連ノート

読み込み中…