Hexamethylphosphoramide → 1-Benzyl-3-methylazetidine-2-carboxylic acid tert-butyl ester

Temperature

0 °C

To a solution of an optically-active compound of [benzyl-(2-chloropropyl)-amino]acetic acid tert-butyl ester (60.0 g) and hexamethyl phosphoramide (36.0 ml) in tetrahydrofuran (360 ml) cooled to −72° C. was added dropwise lithium hexamethyl disilazide (1.0M tetrahydrofuran solution, 242 ml) over 18 minutes, and the mixture was warmed to 0° C. over 80 minutes. To the reaction mixture were sequentially added saturated aqueous ammonium chloride solution (300 ml) and water (400 ml), and the mixture was extracted with ethyl acetate (500 ml). The organic layer was sequentially washed with water (700 ml) and saturated aqueous sodium chloride solution (500 ml), and the separated aqueous layer was extracted with ethyl acetate (300 ml) again. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=50/1 to 4/1) to give the titled compound (50.9 g).

1. extractionthe mixture was extracted with ethyl acetate (500 ml)
2. washThe organic layer was sequentially washed with water (700 ml) and saturated aqueous sodium chloride solution (500 ml)
3. extractionthe separated aqueous layer was extracted with ethyl acetate (300 ml) again
4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=50/1 to 4/1)

ORD record

ord-40a0535cc757445fa912442ef8521a36

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609647B2