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

HRID 336221Notes

Reaction equation

HRID 336221 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]2[C:20]([OH:22])=O)=[CH:9][CH:8]=1.[C:23]([C:27]1[O:31][N:30]=[C:29]([NH2:32])[CH:28]=1)([CH3:26])([CH3:25])[CH3:24]>N1C=CC=CC=1.CCOC(C)=O>[C:23]([C:27]1[O:31][N:30]=[C:29]([NH:32][C:20]([C@@H:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:13]2[C:10]2[CH:9]=[CH:8][C:7]([Cl:6])=[CH:12][CH:11]=2)=[O:22])[CH:28]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 58563924(S)-1-(4-Chloro-phenyl)-azepane-2-carboxylic acid

Product 1

HCID 58563918(S)-1-(4-Chloro-phenyl)-azepane-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phosphorus oxychloride (0.21 g, 1.38 mmol) is added drop wise at 0° C. to a solution of (S)-1-(4-chloro-phenyl)-azepane-2-carboxylic acid (0.23 g, 0.92 mmol) and 5-tert-butyl-isoxazol-3-ylamine (0.19 g, 1.38 mol) in pyridine. The reaction mixture is slowly warmed up to room temperature and stirred for three hours. The mixture is diluted with EtOAc and washed twice with saturated NH4Cl solution. The organic phase is washed with 1N HCl, and after drying over anhydrous Na2SO4 the solvent is removed under reduced pressure to afford the crude product that is purified by prep TLC to afford the title compound; m/z 376 [M+H+].

Workup

  1. washwashed twice with saturated NH4Cl solution
  2. washThe organic phase is washed with 1N HCl
  3. dry with materialafter drying over anhydrous Na2SO4 the solvent
  4. customis removed under reduced pressure
  5. customto afford the crude product that
  6. customis purified by prep TLC

Sources & evidence

ORD record
ord-91ee6462941743acab3a1cc25645ada1
Source dataset
uspto-grants-2014_11
Patent number
US08889670B2

Reaction notes

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