Water → HCID 14650677, compound

HRID 982249Notes

Reaction equation

HRID 982249 reaction equation
[C:1]1([C:7]2[O:8][CH:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:10]([OH:13])[CH2:11][N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[F:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1.O>O1CCCC1>[F:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]([O:13][CH:10]2[CH:9]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[O:8][C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:12][CH2:11]2)=[O:31])=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 709554-Fluorophenyl isocyanateHCID 14650602HCID 14650602, compound

Product 1

HCID 14650677HCID 14650677, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of (5RS, 6SR)-2,6-diphenyl-5,6-dihydro-4H-1,3-oxazin-5-ol (1.52 g) in anhydrous tetrahydrofuran (10 cc) is added at a temperature in the region of 20° C. to an oily suspension (50% by weight; 0.31 g), maintained under an argon atmosphere, of sodium hydride in anhydrous tetrahydrofuran (20 cc). The mixture is stirred for 30 minutes at the same temperature. A solution of 4-fluorophenyl isocyanate (0.9 g) in anhydrous tetrahydrofuran (10 cc) is then added dropwise and stirring is continued for 4 hours at a temperature in the region of 20° C. Distilled water (25 cc) is then added and the mixture is extracted with dichloromethane (3×50 cc). The organic phases are combined, washed with distilled water (3×20 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The residue is purified by chromatography on silica (0.063-0.2 mm; 50 g) contained in a column 2 cm in diameter [eluent: ethyl acetate/cyclohexane (3:7 by volume)], collecting 20-cc fractions. Fractions 3 to 5 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in diisopropyl ether, (5RS, 6SR)-5-(4-fluorophenylcarbamoyloxy)-2,6-diphenyl-5,6-dihydro-4H-1,3-oxazine (0.8 g), m.p. 158° C., is obtained.

Workup

  1. stirringstirring
  2. waitis continued for 4 hours at a temperature in the region of 20° C
  3. extractionthe mixture is extracted with dichloromethane (3×50 cc)
  4. washwashed with distilled water (3×20 cc)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  7. customThe residue is purified by chromatography on silica (0.063-0.2 mm; 50 g)
  8. customcollecting 20-cc fractions
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  10. customAfter recrystallization in diisopropyl ether

Sources & evidence

ORD record
ord-cb62c436f5474b61863f8cc7576556d6
Source dataset
uspto-grants-1991_02
Patent number
US04994569

Reaction notes

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