Pyridine → 4-cyano-N-[2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl]-3-nitrobenzamide

HRID 1970839노트

반응식

HRID 1970839 반응식
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([C:9]([F:18])([C:14]([F:17])([F:16])[F:15])[C:10]([F:13])([F:12])[F:11])[CH:5]=[C:4]([Cl:19])[C:3]=1[NH2:20].[C:21]([C:23]1[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][C:24]=1[N+:32]([O-:34])=[O:33])#[N:22].N1C=CC=CC=1.O=C1N([ClH]P([ClH]N2CCOC2=O)=O)CCO1>ClCCl>[C:21]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([NH:20][C:3]2[C:4]([Cl:19])=[CH:5][C:6]([C:9]([F:18])([C:10]([F:12])([F:13])[F:11])[C:14]([F:15])([F:16])[F:17])=[C:7]([F:8])[C:2]=2[Cl:1])=[O:28])=[CH:25][C:24]=1[N+:32]([O-:34])=[O:33])#[N:22]

참가 물질

5

반응물 3

HCID 1049PyridineHCID 221685834-Cyano-3-nitrobenzoic acidHCID 866652782,6-Dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)-phenylamine

생성물 1

HCID 866652774-cyano-N-[2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl]-3-nitrobenzamide수율 91.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)-phenylamine (Example 3.2) (3.48 g, 10 mmol) and 4-cyano-3-nitrobenzoic acid (made as in WO 2008/074427) (3.84 g, 20 mmol) in dichloromethane (40 ml) was added pyridine (4.17 ml, 30 mmol) and bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”) (5.09 g, 20 mmol). The reaction mixture was heated to reflux for 6 hours. The reaction mixture was cooled to ambient temperature and quenched by addition of aqueous hydrochloric acid (1N) (50 ml). The mixture was then extracted three times with dichloromethane. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 7:3) to give 4-cyano-N-[2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl]-3-nitrobenzamide (4.76 g, 91% yield). LC-MS (Method 2): RT=2.08, [M−H]−=520.

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 6 hours
  3. customquenched by addition of aqueous hydrochloric acid (1N) (50 ml)
  4. extractionThe mixture was then extracted three times with dichloromethane
  5. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 7:3)

출처 및 근거

ORD 기록
ord-6dd833e5368c48348db6785cd072e554
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431514B2

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