Hydrochloric Acid → Dimethyl 6-(difluoromethyl)-4-(iso propylamino)-2-(trifluoromethyl)-3,5-pyridine-dicarboxylate

Participants

Reaction Steps

A mixture of 7.61 g (0.020 mol) of product of Example 63, 6.7 g (0.118 mol) of KOH and 30 ml of H2O in 200 ml of ethanol was refluxed for 16 hours. The reaction mixture was poured into 250 ml containing 50 ml of concentrated HCl, extracted with ether, dried (MgSO4) and concentrated in vacuo to a dark oil. This oil, 5.53 g (0.040 mol) of K2CO3 and 3.75 ml (0.060 mol) of methyl iodide in 50 ml of DMF was stirred at room temperature for 19 hours. The reaction mixture was poured into water, extracted with ether, dried (MgSO4) and concentrated in vacuo to 8.18 g of dark oil. This oil was chromatographed on the HPLC using 5% ethyl acetate/cyclohexane as eluting solvent affording 5.51 g (74.4%) of orange oil. A portion of this oil, 1.41 g, was kugelrohr distilled at 40 Pa, pot temperature 104° C., and 1.37 g of product was collected as a light yellow oil, nD25 1.4765.

Provenance & Evidence