Hydrochloric Acid → HCID 68676230, compound

HRID 644031Notes

Reaction equation

HRID 644031 reaction equation
[CH:1]1([C@H:7]2[NH:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[O:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:17]([O-])=O.[Na+].Cl.[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1>CN(C)C=O.O>[NH2:17][N:12]1[C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[O:9][CH2:8][C@H:7]1[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 23668193Sodium NitriteHCID 68676874HCID 68676874, compound

Product 1

HCID 68676230HCID 68676230, compoundYield 50.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(R)-3-cyclohexyl-3,4-dihydro-2H-1,4-benzoxazine (2.72 g, 12.5 mmol) was dissolved in N,N-dimethylformamide (20 ml) and a solution of sodium nitrite (949 mg, 13.8 mmol) in water (3.0 ml) was added at 0° C. Then, 5 N hydrochloric acid (6.0 ml) was added at 0° C. The reaction mixture was stirred at 0° C. for 1 h, then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The obtained residue was dissolved in diethyl ether (50 ml), and lithium aluminum hydride in tetrahydrofuran (1.0 M; 9.51 ml, 9.51 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 1 h, then quenched with ice water. Ethyl acetate was added to the mixture and the mixture was filtered through a plug of Celite, and the filter cake washed with ethyl acetate. The filtrate was partitioned and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography eluting with 0-17% (v/v) ethyl acetate in heptane to afford (R)-4-amino-3-cyclohexyl-3,4-dihydro-2H-1,4-benzoxazine (1.47 g, 6.33 mmol).

Workup

  1. custompartitioned between ethyl acetate and water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. dissolutionThe obtained residue was dissolved in diethyl ether (50 ml)
  7. stirringThe reaction mixture was stirred at 0° C. for 1 h
  8. customquenched with ice water
  9. additionEthyl acetate was added to the mixture
  10. filtrationthe mixture was filtered through a plug of Celite
  11. washthe filter cake washed with ethyl acetate
  12. customThe filtrate was partitioned
  13. extractionthe aqueous layer extracted with ethyl acetate
  14. washThe combined organic layers were washed with brine
  15. dry with materialdried over sodium sulfate
  16. concentrationconcentrated
  17. customThe residue was purified by flash column chromatography
  18. washeluting with 0-17% (v/v) ethyl acetate in heptane

Sources & evidence

ORD record
ord-d41233627a1145ffb2fdd69a8ca412b3
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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