(Trifluoromethyl)benzene → tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

HRID 1508296노트

반응식

HRID 1508296 반응식
[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9]1([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1)[O:8][CH2:7]2)(=[O:3])[CH3:2].[F:23][C:24]([F:37])([F:36])[C:25]([C:27]1[CH:32]=[C:31]([Cl:33])[C:30](Cl)=[C:29]([Cl:35])[CH:28]=1)=O.C([O-])([O-])=O.[Cs+].[Cs+].[F:44]C(F)(F)C1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:35][C:29]1[CH:28]=[C:27]([C:25]([C:24]([F:37])([F:36])[F:23])=[CH:2][C:1]([C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][CH:12]=2)[C:9]2([CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]2)[O:8][CH2:7]3)=[O:3])[CH:32]=[C:31]([Cl:33])[C:30]=1[F:44]

참가 물질

6

반응물 4

HCID 7368(Trifluoromethyl)benzeneHCID 10796Cesium carbonateHCID 580775942,2,2-Trifluoro-1-(3,4,5-trichlorophenyl)ethan-1-oneHCID 70663143tert-butyl 5'-acetyl-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

생성물 1

HCID 124000325tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate수율 80.64%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
110 °C

실험 절차

In 100 mL two neck RBF equipped with dean-stark apparatus a stirred solution of tert-butyl 5′-acetyl-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 1, 4.5 g, 14.851 mmol) in toluene (13.5 mL) and trifluorotoluene (13.5 mL) was added 2,2,2-trifluoro-1-(3,4,5-trichlorophenyl)-ethanone (4.44 g, 17.079 mmol) and Cs2CO3 (0.483 g, 1.485 mmol) at room temperature. Resulting reaction mixture was heated at 110° C. for 16 hours. After complete consumption of starting material, reaction mixture was diluted with ter-butylmethyl ether (30 mL) and filtered through celite bed. Filtrate was concentrated under vacuum to afford brown sticky oil (9.01 g, crude). Crude compound was purified by column chromatography using silica gel (230-400 mesh). Desired compound was eluted in 20% ethyl acetate in n-hexane to give light yellow solid (6.54 g, 80.64%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 4.10 (d, J=9.52 Hz, 2H), 4.32 (d, J=9.36 Hz, 2H), 5.12 (s, 2H), 7.20 (d, J=9.76 Hz, 2H), 7.39 (s, 1H), 7.56 (d, J=7.96 Hz, 1H), 7.67 (s, 1H), 7.84 (d, J=7.96 Hz, 1H). LC-MS (m/z): 374.1 (M+H).

후처리

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. additionwas diluted with ter-butylmethyl ether (30 mL)
  5. filtrationfiltered through celite bed
  6. concentrationFiltrate was concentrated under vacuum
  7. customto afford brown sticky oil (9.01 g, crude)
  8. customCrude compound was purified by column chromatography
  9. washDesired compound was eluted in 20% ethyl acetate in n-hexane

출처 및 근거

ORD 기록
ord-8ff46c8102624d57bd8c78045b98fa21
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221835B2

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