Hydrochloric Acid → 2-[2-Amino-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

HRID 81565

反応式

HRID 81565 の反応式
[CH3:1][O:2][C:3](=[O:24])[C:4]([O:10][CH2:11][C:12]([N:21]=[N+]=[N-])([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=1)[CH3:13])([CH3:9])[C:5]([F:8])([F:7])[F:6].[In].Cl.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[CH3:1][O:2][C:3](=[O:24])[C:4]([O:10][CH2:11][C:12]([NH2:21])([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=1)[CH3:13])([CH3:9])[C:5]([F:8])([F:7])[F:6]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 5359967IndiumHCID 866502592-[2-Azido-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

生成物 1

HCID 666656742-[2-Amino-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

試薬・触媒・溶媒 1

HCID 21881883Oxolane--water (1/1)溶媒

反応条件

温度
25 °C

実験手順

To a solution of the 2-[2-azido-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester (4.2 g, 9.22 mmol) in THF-H2O 3:1 (48 ml) was added indium (2.116 g, 18.43 mmol) followed by 4N aqueous HCl over a period of 20 min and stirring for 1 h at 25° C. The reaction mixture was added to a 10% aqueous K2CO3 solution and the product was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated. The crude product was purified by flash-chromatography on NEt3 deactivated silica gel (hexane/EtOAc 2:1 to EtOAc) to provide a diastereomeric mixture of the title compound as a yellow oil: TLC (EtOAc): Rf=0.46; HPLC RtH55=0.999 min; 1H NMR (360 MHz, CDCl3): δ 7.73 (s, 1H), 7.47 (d, 1H), 7.41 (d, 1H), 7.24 (t, 1H), 3.84 and 3.83 (s, 3H), 3.59 (s, 2H), 1.61 and 1.59 (s, 3H), 1.52 and 1.51 (s, 3H); ESIMS: 384, 386 [(M+H)+].

後処理

  1. extractionthe product was extracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by flash-chromatography on NEt3 deactivated silica gel (hexane/EtOAc 2:1 to EtOAc)
  7. customto provide

出典と根拠

ORDレコード
ord-3cb9056988fb4cb18b883481526b6c27
出典データセット
uspto-grants-2014_09
特許番号
US08846658B2

関連ノート

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