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

HRID 1508301Notes

Reaction equation

HRID 1508301 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].[Cl:23][C:24]1[CH:25]=[C:26]([C:31](=O)[C:32]([F:35])([F:34])[F:33])[CH:27]=[C:28]([Cl:30])[CH:29]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.FC(F)(F)C1C=CC=CC=1>[Cl:23][C:24]1[CH:25]=[C:26]([C:31]([C:32]([F:35])([F:33])[F:34])=[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:27]=[C:28]([Cl:30])[CH:29]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27582311-(3,5-Dichlorophenyl)-2,2,2-trifluoroethan-1-oneHCID 70663143tert-butyl 5'-acetyl-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Product 1

HCID 90001161tert-butyl 5'-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylateYield 44%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 7368(Trifluoromethyl)benzeneSolvent

Conditions

Temperature
110 °C

Procedure

In 100 mL two neck RBF equipped with dean-stark apparatus, the stirred solution of tert-butyl 5′-acetyl-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 1, 6.65 g, 21.95 mmol) in toluene (20 mL) and trifluorotoluene (20 mL) was added 1-(3,5-dichloro-phenyl)-2,2,2-trifluoro-ethanone (6.133 g, 25.24 mmol) and Cs2CO3 (0.71 g, 2.20 mmol) at room temperature. Resulting reaction mixture was stirred at 110° C. for 16 hours. After complete consumption of starting material, the reaction mixture was diluted with tert-butylmethyl ether (60 mL) and filtered through celite bed. Filtrate was concentrated to get as brown sticky oil (7.2 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 (5.1 g, 43.97%). LC-MS (m/z): 525.9 (M−H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material
  4. additionthe reaction mixture was diluted with tert-butylmethyl ether (60 mL)
  5. filtrationfiltered through celite bed
  6. concentrationFiltrate was concentrated
  7. customto get as brown sticky oil (7.2 g, crude)
  8. customCrude compound was purified by column chromatography
  9. washDesired compound was eluted in 20% ethyl acetate in n-hexane

Sources & evidence

ORD record
ord-9b32e69de5de4989ba94334713c26026
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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