Methyl iodide → HCID 18326588, compound

Participants

Reaction Steps

To a solution of 0.36 g (1.3 mmol) (−)-4-(3,4-Difluorophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester (the product of Example 10, Step C) in 3 ml DMF was added 0.068 g (2.8 mmol) sodium hydride. After the gas evolution had ceased (5 min), 0.10 ml (1.6 mmol) methyl iodide was added and the reaction mixture was stirred 2 hours at room temperature then poured into 100 ml EtOAc and washed 100 ml 5% aqueous KHSO4 solution, 100 ml water, and 100 ml brine; then dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in 5 ml MeOH and to this was added 0.2 ml (0.5 mmol, 2.5M solution in water) NaOH, 2 ml THF, and 0.8 ml (2 mmol, 2.5M solution in water) NaOH. The initially heterogeneous reaction mixture slowly became homogeneous, and after 6 hours, the reaction was poured into 75 ml EtOAc and extracted 2×75 ml H2O. The aqueous layer was acidified to pH=1 with concentrated HCl solution, solid NaCl was added and the mixture extracted 3×50 ml ethyl acetate. The combined ethyl acetate extracts were dried over Na2SO4, filtered and concentrated in vacuo. Toluene (50 ml) was added and removed in vacuo two times, and the residue was dissolved in 1 ml CH2Cl2 and 0.33 g of essentially pure solid was obtained by adding hexane. α25=−150° C.=0.37 MeOH. 1H NMR (300 MHz, CD3OD) d 7.45 (s, 1H); 7.28-7.12 (m, 3H); 5.25 (s, 1H); 3.21 (s, 3H); 2.82 (s, 3H).

Provenance & Evidence