Water → (S)-N-(1-{4-[3-(4-Ethoxy-2-fluoro-phenoxy)-azetidin-1-yl]-phenyl}-ethyl)-acetamide

HRID 40517ノート

反応式

HRID 40517 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11](=[O:13])[CH3:12])[CH3:9])=[CH:4][CH:3]=1.[CH2:14]([O:16][C:17]1[CH:27]=[CH:26][C:20]([O:21][CH:22]2[CH2:25][NH:24][CH2:23]2)=[C:19]([F:28])[CH:18]=1)[CH3:15].C([O-])([O-])=O.[Cs+].[Cs+].O>C1(C)C=CC=CC=1.C(O)(C)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO>[CH2:14]([O:16][C:17]1[CH:27]=[CH:26][C:20]([O:21][CH:22]2[CH2:23][N:24]([C:2]3[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11](=[O:13])[CH3:12])[CH3:9])=[CH:4][CH:3]=3)[CH2:25]2)=[C:19]([F:28])[CH:18]=1)[CH3:15]

参加物

9

反応物 4

HCID 962WaterHCID 10796Cesium carbonateHCID 793484N-((1S)-1-(4-Bromophenyl)ethyl)acetamideHCID 866890183-(4-Ethoxy-2-fluoro-phenoxy)-azetidine

生成物 1

HCID 86689017(S)-N-(1-{4-[3-(4-Ethoxy-2-fluoro-phenoxy)-azetidin-1-yl]-phenyl}-ethyl)-acetamide

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 887Methanol溶媒HCID 1140Toluene溶媒HCID 6386tert-Butanol溶媒

反応条件

温度
120 °C

実験手順

Under an argon atmosphere a mixture of 0.078 g (0.32 mmol) (S)—N-[1-(4-bromo-phenyl)-ethyl]-acetamide (I.1), 0.080 g (0.32 mmol) 3-(4-ethoxy-2-fluoro-phenoxy)-azetidine (see US20090286812), 0.26 g (0.081 mmol) Cs2CO3, 0.0036 g (0.016 mmol) palladium(II) acetate, 0.0077 g (0.016 mmol) 2-dicyclohexylphosphine-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (X-Phos) in 1.5 mL toluene and 0.5 mL tert-butanol is stirred for 12 h at 120° C. Few water and methanol is added, the mixture is filtered and concentrated in vacuo. The residue is purified by HPLC (GeminiCl8, acetone/water (+0.3% NH4OH)) to yield the desired product.

後処理

  1. filtrationthe mixture is filtered
  2. concentrationconcentrated in vacuo
  3. customThe residue is purified by HPLC (GeminiCl8, acetone/water (+0.3% NH4OH))

出典と根拠

ORDレコード
ord-5cef217bbe984c4b953d2a359dfb1fa3
出典データセット
uspto-grants-2013_09
特許番号
US08530461B2

反応ノート

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