Sodium Acetate → (2R,5R)-5-(2-Fluorophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-amine

HRID 221733Notes

Reaction equation

HRID 221733 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C@:8]2([CH3:20])[CH2:13][O:12][C@@:11]([CH3:18])([C:14]([F:17])([F:16])[F:15])[C:10]([NH2:19])=[N:9]2)[CH:7]=1.C([O-])(=O)C.[Na+]>CO.[Pd]>[F:21][C:5]1[CH:4]=[CH:3][CH:2]=[CH:7][C:6]=1[C@:8]1([CH3:20])[CH2:13][O:12][C@@:11]([CH3:18])([C:14]([F:15])([F:16])[F:17])[C:10]([NH2:19])=[N:9]1

Participants

5

Reactant 2

HCID 517045Sodium AcetateHCID 66666066rel-(2R,5R)-5-(5-Bromo-2-fluorophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-amine

Product 1

HCID 66665656(2R,5R)-5-(2-Fluorophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-amine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of (2R,5R)-5-(5-bromo-2-fluoro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (1.66 g, 4.5 mmol) and sodium acetate (0.369 g, 4.5 mmol) in MeOH (50 ml) was hydrogenated over 10% Pd—C for 6 h at 50° C. The catalyst was filtered off over Celite and the filtrate was concentrated. The residue was dissolved in saturated NaHCO3 solution and extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated to provide the title compound as a colorless oil: TLC (hexane-EtOAc 1:1): Rf=0.19; HPLC RtH5=0.777 min; ESIMS: 291 [(M+H)+]; 1H NMR (360 MHz, CDCl3): δ 7.41 (dt, 1H), 7.26 (m, 1H), 7.11 (t, 1H), 7.05 (dd, 1H), 4.11 (dd, 1H), 3.94 (dd, 1H), 1.54 (s, 3H), 1.49 (s, 3H).

Workup

  1. filtrationThe catalyst was filtered off over Celite
  2. concentrationthe filtrate was concentrated
  3. dissolutionThe residue was dissolved in saturated NaHCO3 solution
  4. extractionextracted with EtOAc
  5. washCombined extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e179a80d236849ed8e711d2c21c4489d
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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