Dichloromethane → Difluoro-[4-(3-trifluoromethyl-benzoylamino)-phenyl]-acetic acid ethyl ester

HRID 1818930ノート

反応式

HRID 1818930 の反応式
[CH2:1]([O:3][C:4](=[O:17])[C:5]([F:16])([F:15])[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[CH:8][CH:7]=1)[CH3:2].ClCCl.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26](Cl)=[O:27].CCN(C(C)C)C(C)C>CCOC(C)=O.[Pd].O>[CH2:1]([O:3][C:4](=[O:17])[C:5]([F:16])([F:15])[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][CH:31]=[C:23]([C:22]([F:21])([F:32])[F:33])[CH:24]=2)=[CH:8][CH:7]=1)[CH3:2]

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 10586437Ethyl 2,2-difluoro-2-(4-nitrophenyl)acetate3 回

生成物 1

HCID 68422864Difluoro-[4-(3-trifluoromethyl-benzoylamino)-phenyl]-acetic acid ethyl ester

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Difluoro-(4-nitro-phenyl)-acetic acid ethyl ester (compound 32.1) is reacted according to Sato, K. et. al. Chem. Pharm. Bull. 1999, 47, 1013). Briefly, compound 32.1 and catalytic Pd/C in EtOAc are placed under an atmosphere of hydrogen for 3 hours. The reaction mixture is filtered, concentrated and taken on crude to the next reaction. The crude compound, dichloromethane, 3-(trifluoromethyl)benzoyl chloride and DIEA are stirred at room temperature for 10 minutes. Water is added after which the mixture partitioned between EtOAc and water. The organic layer is separated, washed with brine, dried, filtered and concentrated under reduced pressure. Purification by flash column chromatography on silica gel using a gradient of EtOAc/hexanes provides difluoro-[4-(3-trifluoromethyl-benzoylamino)-phenyl]-acetic acid ethyl ester (compound 32.2).

後処理

  1. filtrationThe reaction mixture is filtered
  2. concentrationconcentrated
  3. customtaken on crude to the next reaction
  4. custompartitioned between EtOAc and water
  5. customThe organic layer is separated
  6. washwashed with brine
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography on silica gel using a gradient of EtOAc/hexanes

出典と根拠

ORDレコード
ord-09cc051c8560489eba71c29024446eb6
出典データセット
uspto-grants-2009_10
特許番号
US07601725B2

反応ノート

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