Methyl iodide → 2-chloro-5-(MethoxyMethyl)pyriMidine

Temperature

0 °C

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 (2.61 g, 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 NH4Cl aq. solution (200 ml), extracted with ether (150 ml×3). The combined organic layers were washed by brine, dried over Na2SO4, 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 6.5 g (66%) of the title compound: MS (ESI) m/z 159.2 (M+H); 1H NMR (500 MHz, CDCl3) δ 8.60 (s, 2H), 4.48 (s, 2H), 3.45 (s, 3H).

1. custom25 min.
2. customat rt
3. temperatureThe reaction mixture was then cooled in ice bath
4. customquenched by addition of saturated NH4Cl aq. solution (200 ml)
5. extractionextracted with ether (150 ml×3)
6. washThe combined organic layers were washed by brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by ISCO column (330 g of silica gel)

ORD record

ord-d02667a540d54f838e6cfc6fd2a68d29

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018224B2