Chloromethyl Methyl Ether → Glycine tert-butyl ester hydrochloride

To the synthesis intermediate of Example 265, that is, tert-butyl 4-hydroxy-3-nitrobenzoate (0.42 g), methylene chloride (10 ml), chloromethylmethylether (0.16 ml), and N,N-diisopropylethylamine (0.37 ml) were added under ice cooling and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with ethyl acetate and successively washed with water, a potassium hydrogensulfate aqueous solution, and saturated saline. The mixture was dried over with anhydrous magnesium sulfate, then concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1). To the obtained tert-butyl 4-methoxymethyloxy-3-nitrobenzoate (0.26 g), ethanol (10 ml) and 10% palladium carbon (40 mg) were added and the mixture was stirred under hydrogen atmosphere at room temperature for 7 hours. The reaction solution was filtered, the filtrate was concentrated, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 1/1). The obtained tert-butyl 3-amino-2-methoxymethyloxybenzoate was used, instead of the starting material compound of Example 220, that is, the glycine tert-butyl ester hydrochloride, for the similar procedure as in Example 220 and Example 245 to obtain the title compound.

1. washsuccessively washed with water
2. dry with materialThe mixture was dried over with anhydrous magnesium sulfate
3. concentrationconcentrated
4. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1)
5. additionTo the obtained tert-butyl 4-methoxymethyloxy-3-nitrobenzoate (0.26 g), ethanol (10 ml) and 10% palladium carbon (40 mg) were added
6. stirringthe mixture was stirred under hydrogen atmosphere at room temperature for 7 hours
7. filtrationThe reaction solution was filtered
8. concentrationthe filtrate was concentrated
9. customthe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 1/1)

ORDレコード

ord-11cc3c46d6d24d4680fbfce24fba8927

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08507714B2