2-chloro-5-(MethoxyMethyl)pyriMidine synthesis

Yield:1416366-34-1 66%

Reaction Conditions:

with sodium hydride in N,N-dimethyl-formamide at 0 - 20; for 0.833333 h;

Steps:

A Preparation of 2-chloro-5-(methoxymethyl)pyrimidine

To a solution of 2-chloro-5-hydroxymethyl-pyrimidine (9.0 g, 62 mmol) in 70 ml of anhydrous DMF was added methyl iodide (6 eq. 370 mmol, 23 ml). The mixture was cooled to 0°C, then NaH (2.6 lg, 1.05 eq.) was added in portions over 5 mins. The resulting mixture was stirred 25 min. at 0°C, then 25 min. at rt. The reaction mixture was then cooled in ice bath, and quenched by addition of saturated NH₄C1 aq. solution (200 ml ), extracted with ether (150 ml x 3). The combined organic layers were washed by brine, dried over Na₂S0₄, filtered and concentrated in vacuo. The residue was purified by ISCO column (330 g of silica gel) using ethyl acetate in hexane (0-90% ethyl acetate, 2500 ml, then 1000 ml of ethyl acetate) to give 6.5g (66%) of the title compound: MS (ESI) mlz 159.2 (M+H); 1H NMR (500 MHz, CDC1₃) δ 8.60 (s, 2H), 4.48 (s, 2H), 3.45 (s, 3H).

References:

WO2013/74388,2013,A1 Location in patent:Page/Page column 44