Dichloromethane → (E)-5-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)-6-oxa-4-azaspiro[2.4]hept-4-en-7-one

HRID 1503791노트

반응식

HRID 1503791 반응식
[F:1][C:2]([F:35])([F:34])[CH:3]([C:25]1[CH:30]=[C:29](Cl)[C:28]([Cl:32])=C(Cl)[CH:26]=1)/[CH:4]=[CH:5]/[C:6]1[CH:20]=[CH:19][C:9]([C:10]([NH:12][C:13]2([C:16]([OH:18])=O)[CH2:15][CH2:14]2)=[O:11])=[C:8]([C:21]([F:24])([F:23])[F:22])[CH:7]=1.CCN=C=NCCCN(C)C.[ClH:47].Cl[CH2:49][Cl:50]>>[F:34][C:2]([F:1])([F:35])[CH:3]([C:25]1[CH:30]=[C:29]([Cl:47])[C:28]([Cl:32])=[C:49]([Cl:50])[CH:26]=1)/[CH:4]=[CH:5]/[C:6]1[CH:20]=[CH:19][C:9]([C:10]2[O:11][C:16](=[O:18])[C:13]3([CH2:15][CH2:14]3)[N:12]=2)=[C:8]([C:21]([F:24])([F:23])[F:22])[CH:7]=1

참가 물질

4

반응물 3

HCID 6344DichloromethaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86722602(E)-1-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)cyclopropanecarboxylic acid

생성물 1

HCID 86722601(E)-5-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)-6-oxa-4-azaspiro[2.4]hept-4-en-7-one수율 73%

실험 절차

A 500 mL rb flask equipped with a magnetic stir bar and a temperature probe was charged with (E)-1-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)cyclopropanecarboxylic acid (9.2 g, 16.41 mmol), dichloromethane (DCM) (30 mL) and cooled in an ice water bath. With stirring, EDC HCl (3.15 g, 16.4 mmol) was added in one portion. After 5 min, the ice bath was removed and the reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was diluted with DCM (100 mL), washed with brine (1×100 mL), dried over sodium sulfate and concentrated. The crude material was purified via an ISCO Rf medium pressure chromatography apparatus using a 330 g normal phase silica gel column and eluting with 0-30% EtOAc/hex gradient to afford the title compound (6.5 g, 73%): 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J=8.1 Hz, 1H), 7.80 (dd, J=1.8, 0.8 Hz, 1H), 7.67 (dd, J=8.2, 1.8 Hz, 1H), 7.42 (s, 2H), 6.66 (d, J=15.9 Hz, 1H), 6.51 (dd, J=15.9, 7.8 Hz, 1H), 4.15 (p, J=8.7 Hz, 1H), 1.99-1.91 (m, 2H), 1.89-1.79 (m, 2H); 19F NMR (376 MHz, CDCl3) δ −59.47, −68.51; ESIMS m/z 544.2 ([M+H]+).

후처리

  1. customA 500 mL rb flask equipped with a magnetic stir bar
  2. temperaturecooled in an ice water bath
  3. customthe ice bath was removed
  4. stirringstirred for 2 h
  5. additionThe reaction mixture was diluted with DCM (100 mL)
  6. washwashed with brine (1×100 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude material was purified via an ISCO Rf medium pressure chromatography apparatus
  10. washeluting with 0-30% EtOAc/hex gradient

출처 및 근거

ORD 기록
ord-f4d8d138bed2413ba9ae48113e773185
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09212164B2

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