Ethyl Acetate → N-(5'-Bromo-4-(difluoromethyl)spiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 539382Notes

Reaction equation

[CH3:1][C:2]([S:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].[Br:8][C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][C:14]3([CH2:23][CH2:22][CH:21]([CH:24]([F:26])[F:25])[CH2:20][CH2:19]3)[C:15]2=O)=[CH:11][CH:10]=1.CCOC(C)=O.C([O-])(O)=O.[Na+]>CCCCCCC.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:8][C:9]1[CH:17]=[C:16]2[C:12](=[CH:11][CH:10]=1)[CH2:13][C:14]1([CH2:23][CH2:22][CH:21]([CH:24]([F:25])[F:26])[CH2:20][CH2:19]1)[C:15]2=[N:7][S:5]([C:2]([CH3:4])([CH3:3])[CH3:1])=[O:6]

Participants

Conditions

Temperature: 90 °C

Procedure

Titanium ethoxide (0.893 mL, 4.33 mmol), 2-methylpropane-2-sulfinamide (0.315 g, 2.60 mmol) and 6′-bromo-4-(difluoromethyl)spiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 91, 0.713 g, 2.17 mmol) were dissolved in 2-Me THF (5 mL) and heated to 90° C. overnight. 2-Methylpropane-2-sulfinamide (0.315 g, 2.60 mmol) and titanium ethoxide (0.893 mL, 4.33 mmol) were added and the reaction was refluxed for 7 h. Another portion of reagents was added and the mixture was refluxed overnight. The reaction was allowed to attain r.t. EtOAc (50 mL) was added followed by dropwise addition of NaHCO3 (10 mL). The mixture was stirred at r.t. for 2 h. The crude product was purified using flash chromatography (40 g SiO2, O-40% EtOAc in heptane) to give the title compound (564 mg, 60% yield): MS (ES+) m/z 432 [M+H]+.

Workup

temperaturethe reaction was refluxed for 7 h
additionAnother portion of reagents was added
temperaturethe mixture was refluxed overnight
customto attain r.t
customThe crude product was purified

Sources & evidence

ORD record: ord-9140d213f7f3431f894431291218d2ff
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865911B2

Reaction notes

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