Potassium Carbonate → (2s)-2-[[5-Chloro-4'-[[(1-ethylpropyl)amino]carbonyl]-3'-fluoro[1,1'-biphenyl]-2-yl]oxy]-propanoic acid

HRID 1023806ノート

反応式

HRID 1023806 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:23])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:16][CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[O:15])=[C:10]([F:22])[CH:9]=2)[CH:7]=1.CC1C=CC(O[C@H:30]([CH3:35])[C:31]([O:33]C)=[O:32])=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][C@@H:30]([CH3:35])[C:31]([OH:33])=[O:32])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:16][CH:17]([CH2:18][CH3:19])[CH2:20][CH3:21])=[O:15])=[C:10]([F:22])[CH:9]=2)[CH:7]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 1540374(R)-Methyl 2-(p-Tolyloxy)propanoateHCID 672768625'-Chloro-n-(1-ethylpropyl)-3-fluoro-2'-hydroxy-[1,1'-biphenyl]-4-carboxamide

生成物 1

HCID 11640118(2s)-2-[[5-Chloro-4'-[[(1-ethylpropyl)amino]carbonyl]-3'-fluoro[1,1'-biphenyl]-2-yl]oxy]-propanoic acid

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
50 °C

実験手順

The product of step c) (300 mg), the product of step d) (219 mg) and potassium carbonate (135 mg) in acetonitrile (10 ml) were charged to a flask and stirred at 50° C. for 16 h. The reaction mixture was cooled, diluted with water (20 ml) and extracted with diethyl ether (3×10 ml). The organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting yellow oil was dissolved in a 1:1 mixture of THF/methanol (10 ml) and 1M NaOH added (1.1 ml). The mixture was stirred at room temperature for 4 h and then concentrated in vacuo. The residue was purified by RPHPLC to give the title compound as a white solid (175 mg).

後処理

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with diethyl ether (3×10 ml)
  3. washThe organic fractions were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting yellow oil was dissolved in a 1:1 mixture of THF/methanol (10 ml) and 1M NaOH
  7. additionadded (1.1 ml)
  8. stirringThe mixture was stirred at room temperature for 4 h
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by RPHPLC

出典と根拠

ORDレコード
ord-7bf227ce523344beac700f7271ba2f16
出典データセット
uspto-grants-2014_05
特許番号
US08722741B2

反応ノート

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