Phenyl isocyanate → (5RS, 6SR)-2-(2-fluorophenyl)-6-phenyl-5-phenylcarbamoyloxy-5,6-dihydro-4H-1,3-oxazine

HRID 982253Notes

Reaction equation

HRID 982253 reaction equation
[C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[O:18][CH:19]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:20]([OH:23])[CH2:21][N:22]=1>ClCCCl>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[O:18][CH:19]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:20]([O:23][C:8](=[O:9])[NH:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:21][N:22]=1

Participants

4

Reactant 2

HCID 7672Phenyl isocyanateHCID 14650610(5RS, 6SR)-2-(2-fluorophenyl)-6-phenyl-5,6-dihydro-4H-1,3-oxazin-5-ol

Product 1

HCID 14650697(5RS, 6SR)-2-(2-fluorophenyl)-6-phenyl-5-phenylcarbamoyloxy-5,6-dihydro-4H-1,3-oxazineYield 39.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Phenyl isocyanate (1 g) is added at a temperature in the region of 20° C. to a solution, maintained under an argon atmosphere, of (5RS, 6SR)-2-(2-fluorophenyl)-6-phenyl-5,6-dihydro-4H-1,3-oxazin-5-ol (2.3 g) in 1,2-dichloroethane (30 cc). The solution obtained is stirred under reflux for 2 hours and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by chromatography on silica (0.063-0.2 mm; 100 g), contained in a column 2.5 cm in diameter [eluent: cyclohexane/ethyl acetate (7:3 by volume)], collecting 20-cc fractions. Fractions 4 to 7 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in ethyl acetate, (5RS, 6SR)-2-(2-fluorophenyl)-6-phenyl-5-phenylcarbamoyloxy-5,6-dihydro-4H-1,3-oxazine (1.3 g), m.p. 128° C., is obtained.

Workup

  1. customThe solution obtained
  2. temperatureunder reflux for 2 hours
  3. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  4. customThe residue is purified by chromatography on silica (0.063-0.2 mm; 100 g)
  5. customcollecting 20-cc fractions
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  7. customAfter recrystallization in ethyl acetate

Sources & evidence

ORD record
ord-f83a79af4fbc473f9dd30f75c2c1739c
Source dataset
uspto-grants-1991_02
Patent number
US04994569

Reaction notes

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