Hydrochloric Acid → 2-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-pyrimidine-5-carboxylic acid

HRID 1095940Notes

Reaction equation

C[O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:32])[C:19]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=3)([OH:24])[C:20]([F:23])([F:22])[F:21])=[C:14]([Cl:33])[CH:13]=2)=[N:9][CH:10]=1)=[O:4].[Li+].[OH-].Cl>C1COCC1.CO>[Cl:33][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[CH:18]([CH3:32])[C:19]([C:25]1[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=1)([OH:24])[C:20]([F:23])([F:21])[F:22])[O:11][C:8]1[N:7]=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:10][N:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

2-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-pyrimidine-5-carboxylic acid methyl ester (27 mg) was dissolved in THF/methanol=5/1 (2.5 mL). The reaction mixture was cooled to 0° C. and aqueous LiOH solution (1.0 M, 0.092 mL) was added. The mixture was stirred at 0° C. for 1 hour. The reaction mixture was poured into ice/water and acidified with 1M aqueous HCl to pH 1. The aqueous phase was then extracted two times with ethyl acetate and the organic layers were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, ethyl acetate:heptane=50:50 to 100:0) to give the title compound as a colorless amorphous foam (2.2 mg, 8.4%). MS (neg. ion, m/e)=486.4 [(M−H)−].

Workup

extractionThe aqueous phase was then extracted two times with ethyl acetate
washthe organic layers were washed with brine
dry with materialdried over Na2SO4
customevaporated
customThe residue was purified by flash chromatography (silica gel, ethyl acetate:heptane=50:50 to 100:0)

Sources & evidence

ORD record: ord-c878d0cb61774f19b182a1d828859223
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138189B2

Reaction notes

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