Hydroxyamine hydrochloride → (+/-)-Isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(5-methyl-isoxazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 507080Notes

Reaction equation

HRID 507080 reaction equation
Cl.[NH2:2]O.[C:4]([O-])(=O)[CH3:5].[Na+].[F:9][C:10]([F:48])([F:47])[C:11]1[CH:12]=[C:13]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)[CH2:14][N:15]([C:34](=[O:39])[CH2:35]C(=O)C)[CH:16]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:18]2[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:17]1=2>CO>[F:47][C:10]([F:9])([F:48])[C:11]1[CH:12]=[C:13]([CH:40]=[C:41]([C:43]([F:44])([F:45])[F:46])[CH:42]=1)[CH2:14][N:15]([C:34]1([CH3:35])[O:39][NH:2][CH:4]=[CH:5]1)[CH:16]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:18]2[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:17]1=2

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 59432322(+/-)-5-[(3,5-Bistrifluoromethyl-benzyl)-(3-oxo-butyryl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylic acid isopropyl ester

Product 1

HCID 86615659(+/-)-Isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(5-methyl-isoxazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 797.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Add hydroxylamine hydrochloride (39 mg, 0.55 mmol) and sodium acetate (1.5 mg, 0.018 mmol). to a solution of compound (+/−)-5-[(3,5-bistrifluoromethyl-benzyl)-(3-oxo-butyryl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylic acid isopropyl ester (Example 51, Step 1) (218 mg, 0.37 mmol) in methanol (1.8 mL) at 0° C., Heat the reaction mixture under reflux overnight. Cool and remove the solvents under reduce pressure. Dilute the residue with ethyl acetate and brine. Separate the layers and dry the organic phase over magnesium sulfate, filter and concentrate in vacuo. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate to afford the title compound (85 mg, 39%). MS (ES+): 590 (M+H).

Workup

  1. temperatureunder reflux overnight
  2. temperatureCool
  3. customremove the solvents
  4. additionDilute the residue with ethyl acetate and brine
  5. customSeparate the layers
  6. dry with materialdry the organic phase over magnesium sulfate
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify the residue by flash chromatography
  10. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-49edfeb8ef9049c48b2016b037b8289d
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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