Hydrochloric Acid → N-methylazetidine-3-carboxamide hydrochloride

To a solution of crude 1-benzhydrylazetidine-3-carboxylic acid methylamide (2.72 g) in methanol (200 ml) were added hydrochloric acid (3.0 ml) and 20% palladium hydroxide carbon (1.0 g), followed by stirring under hydrogen atmosphere (0.40 MPa) for 5 hours. The reaction mixture was filtered to remove the catalyst, which was washed with methanol, and the filtrate was concentrated. To the resultant residue was added hexane, allowed to stand for a while, the supernatant was removed using a pipette. The remain was evaporated to provide a crude product of azetidine-3-carboxylic acid methylamide hydrochloride (ESI-MS (m/z): 115[M+H]+). To the crude product was added water (20 ml), followed by stirring in an ice water bath, and to the reaction mixture were added tetrahydrofuran (10 ml), di-tert-butyl dicarbonate (2.34 g) and sodium hydrogencarbonate (2.25 g), followed by stirring at room temperature for 12.5 hours. The reaction mixture was partitioned between ethyl acetate (200 ml) and brine (50 ml). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:1 to 1:2, ethyl acetate, then ethyl acetate:methanol=10:1 to 5:1) to provide the titled compound (696 mg) as colorless crystals.

1. filtrationThe reaction mixture was filtered
2. customto remove the catalyst, which
3. washwas washed with methanol
4. concentrationthe filtrate was concentrated
5. additionTo the resultant residue was added hexane
6. customthe supernatant was removed
7. customThe remain was evaporated

ORD record

ord-4ae96edb3afe499b936527902ff23639

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07531532B2