Water → HCID 46232856, compound

HRID 1295601Notes

Reaction equation

HRID 1295601 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([C:20](=[O:26])[CH:21](OCC)O)[C:12]2[O:17][CH2:16][C:15](=[O:18])[NH:14][C:13]=2[CH:19]=1)C1C=CC=CC=1.[CH3:27][C:28]([NH2:41])([CH3:40])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=1.[BH4-].[Na+].O>C(O)C.ClCCl>[CH3:40][C:28]([NH:41][CH2:21][CH:20]([C:11]1[C:12]2[O:17][CH2:16][C:15](=[O:18])[NH:14][C:13]=2[CH:19]=[C:9]([OH:8])[CH:10]=1)[OH:26])([CH3:27])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:38])[F:39])[CH:31]=1

Participants

7

Reactant 4

HCID 962WaterHCID 121143Phenethylamine, alpha,alpha-dimethyl-m-trifluoromethyl-HCID 4311764Sodium borohydrideHCID 22063474HCID 22063474, compound

Product 1

HCID 46232856HCID 46232856, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

357 mg (1 mmol) 6-benzyloxy-8-(2-ethoxy-2-hydroxy-acetyl)-4H-benzo[1,4]oxazin-3-one and 217 mg (1 mmol) 1,1-dimethyl-2-(3-trifluoromethyl-phenyl)-ethylamine are stirred for 3 hours in 5 mL ethanol at 65° C. The mixture is cooled to ambient temperature, 113 mg (3 mmol) of sodium borohydride are added and the mixture is stirred overnight. It is combined with 2 mL water, stirred for 30 minutes and then diluted with 10 mL dichloromethane. The solution is filtered through kieselguhr and washed with dichloromethane. The eluate is freed from solvent and the residue is dissolved in 5 mL ethanol and hydrogenated at 2.5 bar and ambient temperature with palladium on charcoal (10%) as catalyst. Then the catalyst is separated off and the crude product is purified by chromatography (reverse phase, acetonitrile/water gradient with 0.1% trifluoroacetic acid). Beige solid. Yield: 169 mg (31%, trifluoroacetate); mass spectroscopy: [M+H]+=425.

Workup

  1. stirringstirred for 30 minutes
  2. filtrationThe solution is filtered through kieselguhr
  3. washwashed with dichloromethane
  4. dissolutionthe residue is dissolved in 5 mL ethanol and hydrogenated at 2.5 bar and ambient temperature with palladium on charcoal (10%) as catalyst
  5. customThen the catalyst is separated off
  6. customthe crude product is purified by chromatography (reverse phase, acetonitrile/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-dfb512e783764e668d424d321dcd493c
Source dataset
uspto-grants-2007_07
Patent number
US07244728B2

Reaction notes

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