Hydrochloric Acid → HCID 117777464, compound

HRID 928544Notes

Reaction equation

HRID 928544 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]([C:23]([O:25][CH3:26])=[O:24])=[C:11]3[C:16]=2[O:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[NH:12]3)=[C:5]([CH3:27])[O:4][N:3]=1.Cl.[N:29]([O-])=[O:30].[Na+]>C(OCC)(=O)C.O>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]([C:23]([O:25][CH3:26])=[O:24])=[C:11]3[C:16]=2[O:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]3[N:29]=[O:30])=[C:5]([CH3:27])[O:4][N:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 23668193Sodium NitriteHCID 117777432HCID 117777432, compound

Product 1

HCID 117777464HCID 117777464, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of methyl 8-(3,5-dimethylisoxazol-4-yl)-3-phenyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylate (0.230 g, 0.631 mmol) in ethyl acetate (6.13 mL) was cooled to 0° C. and treated with 6.0 M hydrogen chloride in water (0.789 mL, 4.73 mmol) and water (0.460 mL) followed by sodium nitrite (0.0871 g, 1.26 mmol) in water (0.690 mL) dropwise. The reaction mixture was stirred at 0° C. for 15 min, the ice bath was removed, and stirred for 30 min which gave a biphasic solution. After another 30 min a suspension was present. The reaction mixture was diluted with EtOAc (40 mL) and water (20 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to give a crude tan solid. Purification by flash column chromatography (100% hexanes to 50% EtOAc/hexanes) gave the desired product (0.228 g, 92%) as a yellow solid. LCMS calculated for C21H20N2O4 ([M−NO]+H)+: m/z=364.1. found: 364.1.

Workup

  1. customthe ice bath was removed
  2. stirringstirred for 30 min which
  3. customgave a biphasic solution
  4. waitAfter another 30 min a suspension was present
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude tan solid
  10. customPurification by flash column chromatography (100% hexanes to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e97c07d37e4448cdb244ba89bacad536
Source dataset
uspto-grants-2016_03
Patent number
US09290514B2

Reaction notes

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