Cesium carbonate → tert-butyl 5'-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

HRID 1508291노트

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HRID 1508291 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:34])=[C:29]([Cl:35])[CH:28]=1)=O.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.FC(C1C=CC=CC=1)(F)F.COC(C)(C)C>[F:37][C:24]([F:23])([F:36])[C:25]([C:27]1[CH:28]=[C:29]([Cl:35])[C:30]([Cl:34])=[C:31]([Cl:33])[CH:32]=1)=[CH:2][C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9]1([CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]1)[O:8][CH2:7]2)=[O:3]

참가 물질

7

반응물 3

HCID 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 90001488tert-butyl 5'-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate수율 66.2%

시약·촉매·용매 3

HCID 1140Toluene용매HCID 7368(Trifluoromethyl)benzene용매HCID 15413tert-Butyl methyl ether용매

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온도
110 °C

실험 절차

In 100 mL two neck RBF fitted with dean-stark apparatus, a stirred solution of tert-butyl 5′-acetyl-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 1, 7 g, 23.1mmol) in toluene (21 mL) and trifluoro methyl benzene (21 mL) was added followed by addition of 2,2,2-trifluoro-1-(3,4,5-trichlorophenyl)ethanone (7.37 g, 26.6 mmol) and Cs2CO3 (0.751 g, 2.31 mmol) at room temperature. Resulting reaction mixture was stirred at 110° C. for 16 hours. Reaction was monitored by TLC, after complete consumption of starting material; reaction mixture was dissolved in tert-butyl methyl ether (50 mL), and filtered through celite bed. The filtrate was concentrated under reduced pressure to get crude compound as brown sticky oil 14.1 g. Purification was done by column chromatography using silica gel 230-400 mesh. Desired compound was eluted in 20% ethyl acetate in n-hexane to give compound as light yellow solid (8.6 g, 66.15%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 4.11 (d, J=9.6 Hz, 2H), 4.32 (d, J=9.52 Hz, 2H), 5.12 (s, 2H), 7.28 (s, 1H), 7.40 (m, 1H), 7.54-7.56 (m, 1H), 7.66 (s, 1H), 7.83 (d, J=7.92 Hz, 1H). VETERINARY (m/z): 560.0 (M−H).

후처리

  1. customResulting
  2. customreaction mixture
  3. customReaction
  4. customafter complete consumption of starting material
  5. customreaction mixture
  6. filtrationfiltered through celite bed
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto get crude compound as brown sticky oil 14.1 g
  9. customPurification
  10. washDesired compound was eluted in 20% ethyl acetate in n-hexane

출처 및 근거

ORD 기록
ord-4d21b0faf759488892f6a1d836d7a276
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221835B2

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