Phosphorus oxychloride → (S)-2-(5-tert-Butyl-isoxazol-3-ylcarbamoyl)-perhydro-azepine-1-carboxylic acid tert-butyl ester

HRID 336215Notes

Reaction equation

HRID 336215 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([O:10][C:11]([N:13]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH:14]1[C:20]([OH:22])=O)=[O:12])([CH3:9])([CH3:8])[CH3:7].[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:6]([O:10][C:11]([N:13]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[C:20](=[O:22])[NH:32][C:29]1[CH:28]=[C:27]([C:23]([CH3:26])([CH3:25])[CH3:24])[O:31][N:30]=1)=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 32920841-[(Tert-butoxy)carbonyl]azepane-2-carboxylic acid

Product 1

HCID 58563977(S)-2-(5-tert-Butyl-isoxazol-3-ylcarbamoyl)-perhydro-azepine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phosphorus oxychloride (0.88 g, 5.73 mmol) is added drop wise at 0° C. to a solution of perhydro-azepine-1,2-dicarboxylic acid 1-tert-butyl ester (0.93 g, 3.82 mmol) and 5-tert-butyl-isoxazol-3-ylamine (0.54 g, 3.82 mol) in pyridine (10.0 mL). 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 used in the next step without further purification; m/z 366 [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

Sources & evidence

ORD record
ord-f0789df63a734aff9ebb4ba04e0e9687
Source dataset
uspto-grants-2014_11
Patent number
US08889670B2

Reaction notes

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