Chloromethyl Methyl Ether → 2-(6-Bromo-pyridin-2-yl)-3-methoxymethoxy-2-methoxymethoxymethyl-propionic acid ethyl ester

HRID 474043Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:17])[C:5]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Br:16])[N:11]=1)([CH2:8][OH:9])[CH2:6][OH:7])[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:27][O:28][CH2:29]Cl.C1[CH2:35][O:34][CH2:33]C1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:3][C:4](=[O:17])[C:5]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([Br:16])[N:11]=1)([CH2:8][O:9][CH2:33][O:34][CH3:35])[CH2:6][O:7][CH2:27][O:28][CH3:29])[CH3:2]

Participants

Conditions

Temperature: 65 °C

Procedure

To the solution of 2-(6-bromo-pyridin-2-yl)-3-hydroxy-2-hydroxymethyl-propionic acid ethyl ester (30.0 g, 98.638 mmol) in dry THF (250 ml) was added tetrabutyl ammonium bromide (15.8 g, 49.319 mmol) and di-isopropyl ethyl amine (127.47 g, 163.0 ml) followed by methoxymethyl chloride was added drop wise at rt. Resultant reaction contents were refluxed at 65° C. for 3 h and cooled to rt. Reaction mixture was concentrated under reduced pressure and purified by column chromatography over silica gel using 10% ethyl acetate in hexane to furnish title compound as a brown liquid. Yield=20.4 g (52%). TLC (30% ethyl acetate in hexane) Rf=0.55; LCMS: RtH7=1.639, [M+1]+=392.0 and 394.0; 1H NMR (400 MHz, CDCl3): δ 7.49 (t, 1H), 7.35 (d, 1H), 7.22 (d, 1H), 4.62-4.47 (m, 4H), 4.24-4.16 (m, 6H), 3.25 (s, 6H), 1.23 (t, 3H).

Workup

additionwas added drop wise at rt
customResultant reaction contents
temperaturecooled to rt
customReaction mixture
concentrationwas concentrated under reduced pressure
custompurified by column chromatography over silica gel using 10% ethyl acetate in hexane

Sources & evidence

ORD record: ord-9c1faedc838044e891d2af5ede8a0938
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637508B2

Reaction notes

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