Water → Tert-butyl 3-fluoro-3-(4-((hydroxyimino)methyl)phenyl)azetidine-1-carboxylate

HRID 1961527Notes

Reaction equation

[F:1][C:2]1([C:13]2[CH:18]=[CH:17][C:16]([CH:19]=O)=[CH:15][CH:14]=2)[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[NH2:21][OH:22].Cl.O>C(O)C>[F:1][C:2]1([C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[N:21][OH:22])=[CH:15][CH:14]=2)[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of tert-butyl 3-fluoro-3-(4-formylphenyl)azetidine-1-carboxylate (Preparation 6, 460 mg, 1.65 mmol) in ethanol (30 mL) was added NH2OH.HCl (127 mg, 1.8 mmol) and water (2.5 mL). The solution was heated to 50° C. for 1 hour and then allowed to stir at room temperature for 2 hours. The reactants were concentrated under vacuum to remove the ethanol. Water (5 mL) was added to the remaining residue and extracted with EtOAc (2×10 mL). Combined organic phases were dried (Na2SO4) and concentrated under vacuum to afford the intermediate as a solid. Yield 485 mg. 1H NMR (CDCl3) δ 8.17 (s, 1H), 7.65 (d, 2H), 7.50 (d, 2H), 5.32 (s, 1H), 4.37-4.50 (m, 2H), 4.28 (m, 2H), 1.45-1.55 (m, 9H). LC/MS retention time=2.926 minutes; MS calculated for (C15H19FN2O3), 294.13; found 195.0 M-Boc.

Workup

concentrationThe reactants were concentrated under vacuum
customto remove the ethanol
additionWater (5 mL) was added to the remaining residue
extractionextracted with EtOAc (2×10 mL)
dry with materialCombined organic phases were dried (Na2SO4)
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-1426f77358a142e880f3d83e4b5398d4
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415310B2

Reaction notes

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