Phosphorus oxychloride → (S)-1-(4-Chloro-phenyl)-azetidine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

HRID 389864Notes

Reaction equation

HRID 389864 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:11][CH2:10][C@H:9]2[C:12]([OH:14])=O)=[CH:4][CH:3]=1.[NH2:15][C:16]1[CH:20]=[C:19]([C:21]([CH3:24])([CH3:23])[CH3:22])[O:18][N:17]=1.P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1.C(OCC)(=O)C>[C:21]([C:19]1[O:18][N:17]=[C:16]([NH:15][C:12]([C@@H:9]2[CH2:10][CH2:11][N:8]2[C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[O:14])[CH:20]=1)([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 67284015(S)-1-(4-Chloro-phenyl)-azetidine-2-carboxylic acid

Product 1

HCID 49847935(S)-1-(4-Chloro-phenyl)-azetidine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cold solution (0° C.) of (S)-1-(4-Chloro-phenyl)-azetidine-2-carboxylic acid (100 mg; 0.472 mmol) and 3-amino-5-t-butylisoxazole (66 mg; 0.472 mmol) in pyridine (1.5 mL) is added phosphorus oxychloride (0.043 m; 0.48 mmol). The reaction mixture is stirred at room temperature for 18 hours. After this time, the reaction mixture is diluted with ethyl acetate and washed with diluted NH4Cl aqueous solution then brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel using ethyl acetate/hexanes provides the title compound, m/z 334 [M+H+].

Workup

  1. washwashed with diluted NH4Cl aqueous solution
  2. dry with materialbrine, dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-b2cc651ec39947a2ba3eca88ae25c82e
Source dataset
uspto-grants-2013_02
Patent number
US08383615B2

Reaction notes

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