3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → Tert-butyl 3-(cyclobutyl(methyl)amino)azetidine-1-carboxylate

HRID 578948Notes

Reaction equation

O=[C:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[CH3:13][NH:14][CH:15]1[CH2:18][CH2:17][CH2:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(OCC)(=O)C>[CH:15]1([N:14]([CH3:13])[CH:2]2[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]2)[CH2:18][CH2:17][CH2:16]1

Participants

Conditions

Temperature: 20 °C

Procedure

Combined a solution of tert-butyl 3-oxoazetidine-1-carboxylate (500 mg, 2.92 mmol) and N-methylcyclobutanamine (0.373 mL, 3.50 mmol) in methylene chloride (15 mL) and added sodium triacetoxyborohydride (929 mg, 4.38 mmol) and the solution stirred at 20° C. for 3 h. The solution was concentrated in vacuo to give a white solid. The solid was taken up in ethyl acetate (50 mL), washed with saturated sodium bicarbonate (50 mL) and brine, dried with magnesium sulfate, and concentrated in vacuo to give a residue which was purified on a 40 g silica gel column eluted with 0 to 70% ethyl acetate in hexanes to give the title compound (342 mg, 1.423 mmol, 48.7%) as a clear, colorless oil. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.43 (s, 9 H) 1.60-1.75 (m, 2 H) 1.85-2.04 (m, 4 H) 2.07 (s, 3 H) 2.81-2.94 (m, 1 H) 3.27-3.30 (m, 1 H) 3.81-3.88 (m, 2 H) 3.88-3.97 (m, 2 H); MS: 241 (M+H).

Workup

concentrationThe solution was concentrated in vacuo
customto give a white solid
washwashed with saturated sodium bicarbonate (50 mL) and brine
dry with materialdried with magnesium sulfate
concentrationconcentrated in vacuo
customto give a residue which
customwas purified on a 40 g silica gel column
washeluted with 0 to 70% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-d0aab9bc68c046e9a20d870474e14651
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040522B2

Reaction notes

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