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 1508291Notes

Reaction equation

HRID 1508291 reaction equation
[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]

Participants

7

Reactant 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

Product 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-carboxylateYield 66.2%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 7368(Trifluoromethyl)benzeneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
110 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4d21b0faf759488892f6a1d836d7a276
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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