O-(propan-2-yl)hydroxylamine hydrochloride → methyl (2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-propan-2-yloxyiminoacetate

Temperature

70 °C

(3-Chloro-4-methanesulfonyl-phenyl)-oxo-acetic acid methyl ester (prepared as in Example 1, 1.30 g, 4.70 mmol) was stirred in methanol (9.5 mL) and warmed in a 70° C. oil bath. O-Isopropyl-hydroxylamine hydrochloride (786 mg, 7.04 mmol) was added. After 7 h, the reaction mixture was allowed to cool and concentrated in vacuo. The residue was dissolved in ethyl acetate (100 mL) and washed with 0.2 M aqueous potassium bisulfate solution (50 mL), 50% aqueous sodium bicarbonate solution (50 mL) and brine (50 mL). The organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes to 33% ethyl acetate/hexanes) afforded (E)-(3-chloro-4-methanesulfonyl-phenyl)-isopropoxyimino-acetic acid methyl ester as a faintly yellow oil contaminated with an unknown impurity (645 mg, <41%): LC-MS (ESI) m/e calcd for C13H16ClNO5S [M+] 333.04, found 334 [M+H+].

1. temperatureto cool
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
4. washwashed with 0.2 M aqueous potassium bisulfate solution (50 mL), 50% aqueous sodium bicarbonate solution (50 mL) and brine (50 mL)
5. dry with materialThe organic phase was dried over magnesium sulfate
6. concentrationconcentrated in vacuo
7. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes to 33% ethyl acetate/hexanes)

ORD record

ord-6bf07104eb47450c9ad90dfd1c024eee

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902248B2