Water → 2-(4-(2-(Difluoromethyl)pyridin-4-yl)phenyl)acetic acid

HRID 592229Notes

Reaction equation

C([O:3][C:4](=[O:26])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([C:18]([F:25])([F:24])C(OCC)=O)[CH:13]=2)=[CH:8][CH:7]=1)C.O>CO.[Li+].[OH-].CN(C=O)C.Cl>[F:25][CH:18]([F:24])[C:14]1[CH:13]=[C:12]([C:9]2[CH:8]=[CH:7][C:6]([CH2:5][C:4]([OH:26])=[O:3])=[CH:11][CH:10]=2)[CH:17]=[CH:16][N:15]=1

Participants

Conditions

Temperature: 55 °C

Procedure

Ethyl 2-(4-(4-(2-ethoxy-2-oxoethyl)phenyl)pyridin-2-yl)-2,2-difluoroacetate 203-4 (476 mg, 1.3 mmol) was dissolved in 5 mL MeOH and 2 mL 2N LiOH. The reaction mixture was stirred at 55° C. for 12 hrs. After cooling to room temperature, the mixture was redissolved in 5 mL DMF and 1.5 mL concentrated HCl. The solution was stirred at 130° C. for 3 hrs. After cooling to room temperature, the solution was poured into 5 ml water and extracted with ethyl acetate (5 mL×3). The combined organic phases were dried over Na2SO4, and concentrated. The residue was purified by silica gel flash chromatography and eluted with 5% MeOH in CH2Cl2 to give 2-(4-(2-(difluoromethyl)pyridin-4-yl)phenyl)acetic acid 203-5. MS m/z 264.1 (M+1).

Workup

temperatureAfter cooling to room temperature
stirringThe solution was stirred at 130° C. for 3 hrs
temperatureAfter cooling to room temperature
extractionextracted with ethyl acetate (5 mL×3)
dry with materialThe combined organic phases were dried over Na2SO4
concentrationconcentrated
customThe residue was purified by silica gel flash chromatography
washeluted with 5% MeOH in CH2Cl2

Sources & evidence

ORD record: ord-8e8af56fde37447489711ddd0864222b
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238646B2

Reaction notes

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