Acetyl chloride → Tert-butyl 3-(5-methyl-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate

HRID 82926Notes

Reaction equation

[NH2:1]/[C:2](=[N:14]\[OH:15])/[CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1.[CH3:16][CH2:17]N(C(C)C)C(C)C.C(Cl)(=O)C>C(#N)C>[CH3:16][C:17]1[O:15][N:14]=[C:2]([CH:3]2[CH2:4][N:5]([C:7]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])[CH2:6]2)[N:1]=1

Participants

Conditions

Temperature: 0 °C

Procedure

In a 16 mL vial, tert-butyl 3-[(Z)-amino(hydroxyimino)methyl]azetidine-1-carboxylate (170 mg, 0.74 mmol; which may be prepared as described in Step 3) was dissolved in acetonitrile (7.4 mL) and cooled to 0° C. under nitrogen. DIPEA (387 μL, 2.22 mmol) and acetyl chloride (105 μL, 1.48 mmol) were added dropwise and the reaction mixture was allowed to warm to room temperature then heated to 80° C. overnight, cooled and concentrated. The residue was taken up in EtOAc and water, the aqueous layer extracted with EtOAc, dried over Na2SO4 and concentrated. The residue was taken up in o-xylene (8.4 mL) and heated to 150° C. for 2 h and concentrated. The crude mixture was purified on column chromatography (eluent: Pentane/EtOAc 7/3) to give the title compound (97 mg, 55%) as an oil.

Workup

temperatureto warm to room temperature
temperaturethen heated to 80° C. overnight
temperaturecooled
concentrationconcentrated
extractionwater, the aqueous layer extracted with EtOAc
dry with materialdried over Na2SO4
concentrationconcentrated
temperatureheated to 150° C. for 2 h
concentrationconcentrated
customThe crude mixture was purified on column chromatography (eluent: Pentane/EtOAc 7/3)

Sources & evidence

ORD record: ord-9de2854d14314b9b9bb9313bef38464a
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846711B2

Reaction notes

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