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

HRID 1818930노트

반응식

HRID 1818930 반응식
[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]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 10586437Ethyl 2,2-difluoro-2-(4-nitrophenyl)acetate3회

생성물 1

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

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-09cc051c8560489eba71c29024446eb6
출처 데이터셋
uspto-grants-2009_10
특허 번호
US07601725B2

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