Triethylamine → Ethyl [5-(trifluoromethyl)pyridin-3-yl]carbonyl carbonate
Reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[N:5][CH:6]=[C:7]([CH:11]=1)[C:8]([OH:10])=[O:9].C(N(CC)CC)C.Cl[C:22]([O:24][CH2:25][CH3:26])=[O:23]>C1COCC1>[C:22](=[O:23])([O:9][C:8]([C:7]1[CH:6]=[N:5][CH:4]=[C:3]([C:2]([F:1])([F:12])[F:13])[CH:11]=1)=[O:10])[O:24][CH2:25][CH3:26]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 5-(trifluoromethyl)nicotinic acid (10.0 g, 52.3 mmol) in THF (250 mL) was added triethyl amine (7.18 mL, 52.3 mmol) at room temperature, then ethyl chloroformate (4.98 mL, 52.3 mmol) was added dropwise at 5° C. slowly. The reaction was stirred for 1 hour to give ethyl [5-(trifluoromethyl)pyridin-3-yl]carbonyl carbonate. NaBH4 (1.702 g, 45.0 mmol) was added to the mixture portionwise at −78° C. followed by addition of MeOH (100 mL) over 30 minutes. The reaction was warmed to 0° C. and stirred overnight. After removal of the solvent, the residue was purified by column chromatography on silica gel eluting with petroleum ether/ethyl acetate=2/1 to give the title compound (5.7 g, 62% yield) as a yellow oil. MS: 178.0 [M+H]+; 1H NMR (400 MHz, CDCl3): δ 8.73 (s, 1H), 8.70 (d, J=1.2 Hz, 1H), 7.92 (d, J=0.4 Hz, 1H), 4.77 (s, 2H), 2.34 (brs, 1H).
Sources & evidence
- ORD record
- ord-5eac0055aa6b42dfa6d9779c63f4fec7
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08772499B2
Reaction notes
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