Hydrochloric Acid → 6-(3-Fluoro-4-methylphenyl)-2-[(2-methylcyclopropyl)methoxy]-4-(trifluoromethyl)nicotinic acid
Reaction equation
[CH3:1][CH:2]1[CH2:4][CH:3]1[CH2:5][OH:6].[H-].[Na+].Cl[C:10]1[N:19]=[C:18]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([F:27])[CH:21]=2)[CH:17]=[C:16]([C:28]([F:31])([F:30])[F:29])[C:11]=1[C:12]([O:14]C)=[O:13].Cl>O1CCCC1>[F:27][C:22]1[CH:21]=[C:20]([C:18]2[CH:17]=[C:16]([C:28]([F:31])([F:29])[F:30])[C:11]([C:12]([OH:14])=[O:13])=[C:10]([O:6][CH2:5][CH:3]3[CH2:4][CH:2]3[CH3:1])[N:19]=2)[CH:25]=[CH:24][C:23]=1[CH3:26]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
37 mg (0.431 mmol) of (2-methylcyclopropyl)methanol and 17 mg (0.431 mmol) of sodium hydride (60% strength dispersion in mineral oil) were initially charged in 5 ml of tetrahydrofuran. The reaction mixture was stirred at room temperature for 60 minutes. 100 mg (0.288 mol) of methyl 2-chloro-6-(3-fluoro-4-methylphenyl)-4-(trifluoromethyl)nicotinate (Example 2A) in 2 ml of tetrahydrofuran were then added. The mixture was stirred at reflux temperature for 3 h and then at room temperature overnight. For work-up, the reaction mixture was adjusted to pH 1 using 1N hydrochloric acid. After removal of the volatile components on a rotary evaporator, the product was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10). This gave 20 mg (18% of theory) of the target compound.
Workup
- stirringThe mixture was stirred
- temperatureat reflux temperature for 3 h
- customat room temperature
- customovernight
- customAfter removal of the volatile components
- customon a rotary evaporator
- customthe product was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10)
Sources & evidence
- ORD record
- ord-d2dbbee8ad02448c80a06b299ad82da6
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08143411B2
Reaction notes
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