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

HRID 1486002Notes

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), δ, 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-d4d0ad9b896649bb8a31284dcad68483
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422310B2

Reaction notes

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