Nicotinate → 6-(1-(4'-(Trifluoromethyl)biphenyl-4-yloxy)ethyl)nicotinic acid

HRID 2406964Notes

Reaction equation

[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[H-].[Na+].[C:20]([O-:28])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[N:23][CH:22]=1.O1CC[CH2:31][CH2:30]1>CS(C)=O>[F:1][C:2]([F:16])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:30]([C:24]3[CH:25]=[CH:26][C:21]([C:20]([OH:28])=[O:27])=[CH:22][N:23]=3)[CH3:31])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a 0° C. solution of 4′-(trifluoromethyl)biphenyl-4-ol (263 mg, 1.1 mmol) in tetrahydrofuran (6 mL) was added sodium hydride (44.2 mg, 60 wt % in mineral oil, 1.1 mmol). The reaction mixture was stirred at 0° C. for 30 minutes. A solution of the crude methyl 641-(methylsulfonyloxy)ethyl)nicotinate prepared above in DMSO (6 mL) was added. The mixture was heated to 60° C. for 48 hours. The mixture was quenched with water and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered and concentrated to give 6-(1-(4′-(trifluoromethyl)biphenyl-4-yloxy)ethyl)nicotinic acid (60 mg). 1H NMR (400 MHz, CD3OD, δ): 8.98 (m, 1H), 8.19-8.21 (m, 1H), 7.54-7.61 (m, 4H), 7.42-7.44 (m, 3H), 6.86-6.89 (m, 1H), 5.42-4.43 (q, 1H), 1.58 (d, 9H).

Workup

additionwas added
temperatureThe mixture was heated to 60° C. for 48 hours
customThe mixture was quenched with water
extractionextracted with dichloromethane
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-18451c3515894cd9a7ec7ac97f5243c1
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809342B2

Reaction notes

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