Methanamine, N-methoxy-, hydrochloride (1:1) → 4-(4-Fluoro-phenyl)-4-methyl-pentanoic acid methoxy-methyl-amide

HRID 1026124Notes

Reaction equation

C(O[C:4](=[O:17])[CH2:5][CH2:6][C:7]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)([CH3:9])[CH3:8])C.Cl.[CH3:19][NH:20][O:21][CH3:22].C([Mg]Cl)(C)C>O1CCCC1>[CH3:22][O:21][N:20]([CH3:19])[C:4](=[O:17])[CH2:5][CH2:6][C:7]([C:10]1[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=1)([CH3:8])[CH3:9]

Participants

Conditions

Temperature: -15 °C

Procedure

To a stirred solution of 4-(4-fluoro-phenyl)-4-methyl-pentanoic acid ethyl ester (3.97 g) and N,O-dimethylhydroxylamine hydrochloride (2.44 g) in tetrahydrofuran (40 ml) at −18° C. was added dropwise a solution of isopropylmagnesium chloride (25.0 ml, 2 M solution in THF). The mixture was stirred for 30 min at −15° C. and then quenched by addition of saturated ammonium chloride solution. The mixture was then acidified to pH 1 by addition of 1 M aq. hydrochloric acid and taken up in ethyl acetate. The mixture was washed sequentially with water and with saturated brine, then dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (SiO2, heptane/EtOAc gradient) to yield a colourless oil, (3.91 g, 93%); MS (ISP): 254.2 ([M+H]+).

Workup

customquenched by addition of saturated ammonium chloride solution
additionThe mixture was then acidified to pH 1 by addition of 1 M aq. hydrochloric acid
washThe mixture was washed sequentially with water and with saturated brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (SiO2, heptane/EtOAc gradient)
customto yield a colourless oil, (3.91 g, 93%)

Sources & evidence

ORD record: ord-511d620eb24b4688878750b84d784df4
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729113B2

Reaction notes

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