Ammonium Chloride → 1-(3,5-difluorophenyl)-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropan-1-ol

HRID 1274881Notes

Reaction equation

HRID 1274881 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[CH:5]=[C:6]([F:8])[CH:7]=1.[Mg].[CH3:11][C:12]1[O:17][CH2:16][N:15]([C:18]([CH3:22])([CH3:21])[CH:19]=[O:20])[C:14](=[O:23])[C:13]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:19]([OH:20])[C:18]([CH3:21])([N:15]2[C:14](=[O:23])[C:13]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:12]([CH3:11])[O:17][CH2:16]2)[CH3:22])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 1363131-Bromo-3,5-difluorobenzeneHCID 5462224MagnesiumHCID 221182842-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropionaldehyde

Product 1

HCID 221183241-(3,5-difluorophenyl)-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropan-1-olYield 35.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

3,5-Difluorobromobenzene (2.9 g) was added to a suspension of magnesium (0.41 g) in tetrahydrofuran, under an inert atmosphere at 20° C., slowly, to initiate reaction, then at a rate to maintain gentle reflux. After refluxing for 1 hour, the mixture was added to a solution of 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropionaldehyde (2.59 g) in tetrahydrofuran at -78° C. The solution was warmed to ambient temperature and stirred for 18 hours. Ammonium chloride and ethyl acetate were added and the organic phase dried (magnesium sulphate) and evaporated to give 1-(3,5-difluorophenyl)-2-methyl-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-propan-1-ol (1.32 g), m.p. 87.6-89.0° C.

Workup

  1. customreaction
  2. temperatureat a rate to maintain gentle reflux
  3. temperatureAfter refluxing for 1 hour
  4. dry with materialthe organic phase dried (magnesium sulphate)
  5. customevaporated

Sources & evidence

ORD record
ord-0a1a1590124c4640a8f5800d02d5f698
Source dataset
uspto-grants-2000_12
Patent number
US06159902

Reaction notes

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