Sodium hydride → HCID 58174182, compound

HRID 1255890Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

To a suspension of NaH (60% dispersion in oil; 1.2 g, 30 mmol) in 30 mL of DMSO was added a solution of 4-(trifluoromethyl)phenol (1.86 g, 30 mmol) in 20 mL of DMSO and the mixture was stirred for 30 min. To this was added methyl 6-chloronicotinate (5.13 g, 30 mmol) and the solution was heated overnight at 70° C. The reaction was cooled to room temperature and then diluted with Et2O. The solution was washed with H2O, brine, dried with Na2SO4, suction filtered, and the solvent removed in vacuo. The residue was purified via normal phase column chromatography over SiO2 using 15% Et2O/pentane to yield 6-(4-trifluoromethylphenoxy)-nicotinic acid methyl ester (4.5 g) as a colorless solid: 1H-NMR (300 MHz, CDCl3) δ 8.81 (dd, J=2.5, 0.6 Hz, 1H), 8.33 (dd, J=8.6, 2.4 Hz, 1H), 7.69 (d, J=8.5 Hz, 2H), 7.31-7.24 (m, 2H), 7.02 (dd, J=8.5, 0.6 Hz, 1H), 3.93 (s, 3H); EIMS m/z 297 ([M]+).

Workup

temperatureThe reaction was cooled to room temperature
washThe solution was washed with H2O, brine
dry with materialdried with Na2SO4, suction
filtrationfiltered
customthe solvent removed in vacuo
customThe residue was purified via normal phase column chromatography over SiO2 using 15% Et2O/pentane

Sources & evidence

ORD record: ord-966fb0417b9642bb9a900d237a2f6b15
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461164B2

Reaction notes

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