Water → HCID 67928944, compound

HRID 982284Notes

Reaction equation

HRID 982284 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][CH2:11][CH:12]([OH:21])[CH:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:14]=2)=[CH:5][CH:4]=1.[H-].[Na+].[Cl:24][C:25]1[CH:26]=[C:27]([N:32]=[C:33]=[O:34])[CH:28]=[CH:29][C:30]=1[Cl:31].O>O1CCCC1>[Cl:24][C:25]1[CH:26]=[C:27]([NH:32][C:33]([O:21][CH:12]2[CH2:11][O:10][C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)=[N:14][CH:13]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:34])[CH:28]=[CH:29][C:30]=1[Cl:31]

Participants

6

Reactant 4

HCID 962WaterHCID 76073,4-Dichlorophenyl isocyanateHCID 24758Sodium hydrideHCID 14650600HCID 14650600, compound

Product 1

HCID 67928944HCID 67928944, compoundYield 46.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of (4RS, 5RS)-2-(4-methoxyphenyl)-4-phenyl-5,6-dihydro-4H-1,3-oxazin-5-ol (1.42 g) in anhydrous tetrahydrofuran (15 cc) is added at a temperature in the region of 20° C. to an oily suspension (50% by weight; 0.27 g), maintained under an argon atmosphere, of sodium hydride in anhydrous tetrahydrofuran (15 cc), and the solution obtained is stirred for 30 minutes at this same temperature. A solution of 3,4-dichlorophenyl isocyanate (1.05 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 (20 cc) is then added and the mixture is extracted with dichloromethane (3×80 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 solid obtained is purified by chromatography on silica (0.063-0.2 mm; 300 g) contained in a column 3.5 cm in diameter (eluent: dichloromethane), collecting 30 cc fractions. Fractions 4 to 7 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The solid obtained is again purified by chromatography on silica (0.063-0.2 mm; 125 g) contained in a column 2 cm in diameter [eluent: cyclohexane/ethyl acetate (6:4 by volume)], collecting 20-cc fractions. The fractions 5 to 9 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in diisopropyl ether, (4RS, 5RS)-5-(3,4-dichlorophenylcarbamoyloxy)-2-(4-methoxyphenyl)-4-phenyl-5,6-dihydro-4H-1,3-oxazine (1.1 g), m.p. 130° C., is obtained.

Workup

  1. customthe solution obtained
  2. stirringstirring
  3. waitis continued for 4 hours at a temperature in the region of 20° C
  4. extractionthe mixture is extracted with dichloromethane (3×80 cc)
  5. washwashed with distilled water (3×20 cc)
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  8. customThe solid obtained
  9. customis purified by chromatography on silica (0.063-0.2 mm; 300 g)
  10. customcollecting 30 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  12. customThe solid obtained
  13. customis again purified by chromatography on silica (0.063-0.2 mm; 125 g)
  14. customcollecting 20-cc fractions
  15. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  16. customAfter recrystallization in diisopropyl ether

Sources & evidence

ORD record
ord-68a85e6f88de4047b9f5f3fa602932c0
Source dataset
uspto-grants-1991_02
Patent number
US04994569

Reaction notes

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