Stannane, hydroxytrimethyl- → 4-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid

HRID 448937Notes

Reaction equation

C[O:2][C:3](=[O:25])[C:4]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][C:13]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:15]=2[C:16]#[N:17])[C:7]([Cl:22])=[CH:6][C:5]=1[O:23][CH3:24].[OH-].C[Sn+](C)C>ClCCCl>[Cl:22][C:7]1[C:8]([C:10]2[CH:11]=[N:12][C:13]([C:18]([F:19])([F:21])[F:20])=[CH:14][C:15]=2[C:16]#[N:17])=[CH:9][C:4]([C:3]([OH:25])=[O:2])=[C:5]([O:23][CH3:24])[CH:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid methyl ester (1.2 g, 3.2 mmol) and trimethyltin hydroxide (1.75 g, 9.7 mmol) in 1,2-dichloroethane (50 mL) was heated to 80° C. in a sealed tube for 4 hrs. Additional 5.0 eq. of trimethyltin hydroxide was added and the mixture was heated for total of 48 hrs. The mixture was then cooled to rt, quenched with HCl (2N, 40 mL) and diluted with 1,2-dichloroethane. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The residue was purified via silica gel flash column chromatography eluting with dichloromethane:methanol (9:1) to afford 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid (723 mg). NMR (CDCl3), 5, 8.82 (1H, s), 7.94 (1H, s), 7.81 (1H, s), 7.20 (1H, s), 3.90 (3H, s).

Workup

temperaturethe mixture was heated for total of 48 hrs
temperatureThe mixture was then cooled to rt
customquenched with HCl (2N, 40 mL)
additiondiluted with 1,2-dichloroethane
customThe organic layer was separated
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified via silica gel flash column chromatography
washeluting with dichloromethane:methanol (9:1)

Sources & evidence

ORD record: ord-1dd40625bd58479cbaec40b240d8078e
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481738B2

Reaction notes

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