Hydrogen iodide → Methyl 4-amino-2-(trifluoromethyl)nicotinate
Reaction equation
I.[N:2]([C:5]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([C:15]([F:18])([F:17])[F:16])[N:8]=[CH:7][CH:6]=1)=[N+]=[N-]>ClCCl>[NH2:2][C:5]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([C:15]([F:18])([F:16])[F:17])[N:8]=[CH:7][CH:6]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Cold (0° C. ice bath) concentrated hydriodic acid (182 mL of a 57% aqueous solution) is added to methyl 4-azido-2-(trifluoromethyl)nicotinate (7.50 g, 30.5 mmol) in a flask. The mixture is stirred at 0° C. until TLC (ethyl acetate-hexanes, 75:25) shows complete consumption of starting material. The mixture is poured over an ice cold solution of potassium hydroxide (95 g of solid KOH dissolved in 300 mL of water). The mixture is extracted with diethyl ether. The ethereal layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a yellow solid. The solid is dissolved in a minimal amount of dichloromethane and passed through a silica gel plug, eluting with ethyl acetate-hexanes (10:90). The eluant is concentrated to afford 3.42 g (51%) of methyl 4-amino-2-(trifluoromethyl)nicotinate as an off-white solid. 1HNMR (400 MHz, CD3OD), 8.11 (d, 1H), 6.93 (d, 1H), 3.878 (s, 3H). LC/MS (M+1)=221.2