Water → HCID 68677380, compound

HRID 500441Notes

Reaction equation

HRID 500441 reaction equation
[CH:1]1([C@H:7]2[N:12]3[C:13](C(OCC)=O)=[CH:14][C:15]4[CH:16]=[CH:17][CH:18]=[C:10]([C:11]=43)[O:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].C(OCC)(=O)C.O>C(O)C.[Cu]>[CH:1]1([C@H:7]2[N:12]3[CH:13]=[CH:14][C:15]4[CH:16]=[CH:17][CH:18]=[C:10]([C:11]=43)[O:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 86612015HCID 86612015, compound

Product 1

HCID 68677380HCID 68677380, compoundYield 85.7%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl (R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-5-carboxylate (1.49 g, 4.76 mmol) in ethanol (50 ml) was added 4 N sodium hydroxide (5.94 ml, 23.8 mmol). The mixture was stirred at 70° C. for 40 min. Ethanol was removed in vacuo, and the residue was neutralised with 2 N hydrochloric acid, and partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane and the combined organic layers washed with brine, dried over sodium sulfate and concentrated. The residue was dissolved in quinoline (20 ml), then copper powder (453 mg, 7.13 mmol) was added. The mixture was stirred at 210° C. for 1 h. Ethyl acetate and water were added to the mixture at room temperature, and the mixture was filtered through a plug of Celite, and the filter cake washed with ethyl acetate. The filtrate was acidified with 5 N hydrochloric acid and partitioned. The aqueous layer was extracted with ethyl acetate and the combined organic layers washed with 1 N hydrochloric acid and brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography eluting with 0-10% (v/v) ethyl acetate in heptane to afford (R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine (984 mg, 4.08 mmol).

Workup

  1. customEthanol was removed in vacuo
  2. custompartitioned between dichloromethane and water
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washthe combined organic layers washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in quinoline (20 ml)
  8. stirringThe mixture was stirred at 210° C. for 1 h
  9. filtrationthe mixture was filtered through a plug of Celite
  10. washthe filter cake washed with ethyl acetate
  11. custompartitioned
  12. extractionThe aqueous layer was extracted with ethyl acetate
  13. washthe combined organic layers washed with 1 N hydrochloric acid and brine
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. customThe residue was purified by flash chromatography
  17. washeluting with 0-10% (v/v) ethyl acetate in heptane

Sources & evidence

ORD record
ord-334065819c4c40678a0322d702b6dff3
Source dataset
uspto-grants-2010_08
Patent number
US07772227B2

Reaction notes

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