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Potassium Carbonate → 4'-((R)-1-tert-Butoxycarbonylamino-ethyl)-3-chloro-3'-fluoro-biphenyl-2-carboxylic acid methyl ester

HRID 1404543
ノート
印刷プレビュー

反応式

HRID 1404543 の反応式
[C:1]([O:5][C:6](=[O:26])[NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][C:11]=1[F:25])[CH3:9])([CH3:4])([CH3:3])[CH3:2].Br[C:28]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:29]=1[C:30]([O:32][CH3:33])=[O:31].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:33][O:32][C:30]([C:29]1[C:28]([C:13]2[CH:14]=[CH:15][C:10]([C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:26])[CH3:9])=[C:11]([F:25])[CH:12]=2)=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:38])=[O:31]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 2759827Methyl 2-bromo-6-chlorobenzoateHCID 16102905{(R)-1-[2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-carbamic acid tert-butyl ester2 回

生成物 1

HCID 161028894'-((R)-1-tert-Butoxycarbonylamino-ethyl)-3-chloro-3'-fluoro-biphenyl-2-carboxylic acid methyl ester

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of {(R)-1-[2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-carbamic acid tert-butyl ester (600 mg, 1.64 mmol, intermediate 13), methyl 2-bromo-6-chlorobenzoate (430 mg, 1.72 mmol) [CAS 685892-23-3; commercially available], tri-o-tolyl-phosphane (100 mg, 329 μmol), potassium carbonate (568 mg, 4.11 mmol) and palladium(II) acetate (18.4 mg, 82.1 μmol) in THF (20.0 ml) and water (1.18 ml) was stirred at room temperature over night. The reaction mixture was diluted with water and extracted three times with EtOAc. The combined extracts were washed with water and brine, dried with Na2SO4 and concentrated in vacuo. The remaining residue was purified by chromatography (silica gel; DCM/EtOAc 100:0-90:10) and the title compound was obtained as colorless oil (385 mg, 58%). MS: 466.1 [M−H+OAc]−.

後処理

  1. extractionextracted three times with EtOAc
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe remaining residue was purified by chromatography (silica gel; DCM/EtOAc 100:0-90:10)

出典と根拠

ORDレコード
ord-25c274ec78ec4e9d9b610ddfaead1434
出典データセット
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08912221B2

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