Dichloromethane → HCID 13995480, compound

Temperature

-78 °C

(R)-3-Hydroxy-2-methyl-propionic acid methyl ester (8.60 g, 0.0728 mol) was dissolved in methylene chloride (200 mL, 3 mol), followed by N,N-diisopropylethylamine (25.4 mL, 0.146 mol). The reaction mixture was then cooled to −78° C., and chloromethyl methyl ether (9.48 mL, 0.0874 mol) was added dropwise. The reaction mixture was then allowed to warm up gradually over for 5 hours to 23° C., and quenched with Na2CO3 (sat). Organic layer was separated, and washed with water, brine, and then dried over Na2SO4. The to crude mixture was purified via chromatography (SiO2, 120g, 0-30% ethyl acetate/hexanes) to give 10.3 g clear liquid product (87%). 1H NMR (CHLOROFORM-d) δ: 4.61 (s, 2H), 3.71 (m, 4H), 3.58 (dd, J=9.5, 5.5 Hz, 1H), 3.35 (s, 3H), 2.77 (m, 1H), 1.19 (d, J=7.0 Hz, 3H).

1. temperatureto warm up gradually over for 5 hours to 23° C.
2. customquenched with Na2CO3 (sat)
3. customOrganic layer was separated
4. washwashed with water, brine
5. dry with materialdried over Na2SO4
6. customThe to crude mixture was purified via chromatography (SiO2, 120g, 0-30% ethyl acetate/hexanes)

ORD record

ord-f12ded3e501c41fda6f078ce394a4578

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349849B2