Silane, ((1-methoxy-2-methyl-1-propenyl)oxy)trimethyl- → methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-hydroxy-2,2,5-trimethylhexanoate

HRID 563413Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17](=[O:22])[CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:23][O:24][C:25]([O:29][Si](C)(C)C)=[C:26]([CH3:28])[CH3:27]>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([OH:22])([CH2:18][CH:19]([CH3:20])[CH3:21])[C:26]([CH3:28])([CH3:27])[C:25]([O:24][CH3:23])=[O:29])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1-(1-(4-Fluorophenyl)-1H-indazol-5-yl)-3-methylbutan-1-one (220 mg, 0.742 mmol) was dissolved in 10 mL of dry DCM and 1-methoxy-2-methyl-1-(trimethylsiloxy)propene (0.162 mL, 0.8 mmol) was added. The reaction mixture was cooled to 0° C. and TiCl4 (0.8 mL of 1.0 M DCM solution, 0.8 mmol) was added portionwise and then stirred 12 h. The reaction was quenched with aqueous sodium bicarbonate and extracted 2×DCM. The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified SiO2 chromatography eluting with 1:1 EtOAc/hexane to give 280 mg (95% yield) of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-hydroxy-2,2,5-trimethylhexanoate. MS found: (M+H)+=399.

Workup

customThe reaction was quenched with aqueous sodium bicarbonate
extractionextracted 2×DCM
dry with materialThe organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified SiO2 chromatography
washeluting with 1:1 EtOAc/hexane

Sources & evidence

ORD record: ord-a3d066bba62944deb71c34b5c0901fa6
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067447B2

Reaction notes

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