Hydrochloric Acid → 6-[(Acetyloxy)methyl]-2-(trifluoromethyl)pyrimidine-4-carboxylic acid
Reaction equation
[C:1]([O:4][CH2:5][C:6]1[N:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[N:9]=[C:8]([C:16]([O:18]CC)=[O:17])[CH:7]=1)(=[O:3])[CH3:2].O.[OH-].[Li+].Cl>O1CCCC1.O>[C:1]([O:4][CH2:5][C:6]1[N:11]=[C:10]([C:12]([F:13])([F:15])[F:14])[N:9]=[C:8]([C:16]([OH:18])=[O:17])[CH:7]=1)(=[O:3])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A solution of ethyl 6-[(acetyloxy)methyl]-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.95 g, 3.2 mmol, from Step B) in tetrahydrofuran (8.7 mL) at 0° C. was treated with lithium hydroxide, monohydrate (140 mg, 3.2 mmol) in water (1.3 mL). The reaction was stirred for 15 minutes, then was treated with 1N HCl to pH4 while still in the ice bath. THF was removed from the mixture in vacuo. The product was extracted first with ethyl acetate, then with several portions of 10% iPrOH in CHCl3, including periodic adjustment of pH as necessary. The extracts were combined and dried over sodium sulfate, filtered and concentrated to afford a yellow oil, which was used without further purification (0.86 g, 100%). 1H NMR (300 MHz, CDCl3): δ 8.25 (s, 1H), 5.35 (s, 2H), 2.23 (s, 3H); LCMS (M+H)+: 265.0.
Workup
- customTHF was removed from the mixture in vacuo
- extractionThe product was extracted first with ethyl acetate
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customto afford a yellow oil, which
- customwas used without further purification (0.86 g, 100%)
Sources & evidence
- ORD record
- ord-9759d114b37246d9b2ed9ad6527c512f
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08933085B2
Reaction notes
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