Water → N-(5'-((3,3-Difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 1468074Notes

Reaction equation

[F:1][C:2]1([F:25])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)[C:14]3=O)=[CH:10][CH:9]=2)[CH2:3]1.[CH3:26][C:27]([S:30]([NH2:32])=[O:31])([CH3:29])[CH3:28].O>C(OCC)(=O)C.C(O[Ti](OCC)(OCC)OCC)C>[F:25][C:2]1([F:1])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11](=[CH:10][CH:9]=2)[CH2:12][C:13]2([CH2:18][CH2:19][CH:20]([O:23][CH3:24])[CH2:21][CH2:22]2)[C:14]3=[N:32][S:30]([C:27]([CH3:29])([CH3:28])[CH3:26])=[O:31])[CH2:3]1

Participants

Conditions

Temperature: 80 °C

Procedure

6′-((3,3-Difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 14, 1.85 g, 5.28 mmol) and 2-methylpropane-2-sulfinamide (1.15 g, 9.50 mmol) were dissolved in 2-Me THF (40 mL). Tetraethoxytitanium (2.21 mL, 10.6 mmol) was added and the resulting mixture was heated to 80° C. over a weekend. The reaction mixture was cooled to r.t., and diluted with ethyl acetate (85 mL). Water (3 mL) was added under vigorous stirring and then the mixture was allowed to stand for 1 h. The mixture was filtered, the solvent was evaporated and the residue was purified by column chromatography on silica using a gradient of 0-70% ethyl acetate in heptanes. The product was recrystallized twice from EtOH. to give 0.750 g of the title compound (31% yield). MS (ES+) m/z 454 [M+H]+.

Workup

temperatureThe reaction mixture was cooled to r.t.
filtrationThe mixture was filtered
customthe solvent was evaporated
customthe residue was purified by column chromatography on silica using a gradient of 0-70% ethyl acetate in heptanes
customThe product was recrystallized twice from EtOH

Sources & evidence

ORD record: ord-7cd20821c2bc4d598944eaa3eb2446aa
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09000185B2

Reaction notes

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