Ammonium Chloride → HCID 86566740, compound

HRID 928545Notes

Reaction equation

HRID 928545 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]([C:25]([O:27]C)=O)=[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:23]=O)=[C:5]([CH3:29])[O:4][N:3]=1.[Cl-].[NH4+]>C(OCC)(=O)C.CO.[Zn]>[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][CH:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:12]4[C:11]=3[C:10]([C:25](=[O:27])[NH:23]4)=[CH:9][CH:8]=2)=[C:5]([CH3:29])[O:4][N:3]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 117777464HCID 117777464, compound

Product 1

HCID 86566740HCID 86566740, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of methyl 8-(3,5-dimethylisoxazol-4-yl)-4-nitroso-3-phenyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylate (0.228 g, 0.580 mmol) in ethyl acetate (4.04 mL) and methanol (4.04 mL) at 0° C. was treated with saturated aqueous ammonium chloride solution (2.02 mL, 30.2 mmol) and then zinc (0.303 g, 4.64 mmol) was added in three portions over 6 min. The cooling bath was removed and the reaction mixture was stirred for 2 h. The reaction mixture was diluted with ethyl acetate (30 mL), filtered through a Celite pad, and rinsed with ethyl acetate (2×10 mL). The filtrate was washed with water (20 mL), brine, (20 mL), dried over sodium sulfate, filtered, and concentrated to give a crude tan foam. Purification by flash column chromatography (100% dichloromethane to 10% methanol/dichloromethane) gave the desired product (0.14 g, 70%) as a yellow foam. 1H NMR (500 MHz, DMSO-d6) δ 10.98 (br s, 1H), 7.40-7.29 (m, 3H), 7.26 (d, J=8.3 Hz, 1H), 7.23-7.15 (m, 2H), 6.87 (d, J=8.2 Hz, 1H), 5.39 (br s, 1H), 4.74 (dd, J=11.5, 3.1 Hz, 1H), 4.61 (dd, J=11.5, 5.8 Hz, 1H), 2.31 (s, 3H), 2.15 (s, 3H). LCMS calculated for C20H18N3O3 (M+H)+: m/z=348.1. found: 348.1.

Workup

  1. customThe cooling bath was removed
  2. additionThe reaction mixture was diluted with ethyl acetate (30 mL)
  3. filtrationfiltered through a Celite pad
  4. washrinsed with ethyl acetate (2×10 mL)
  5. washThe filtrate was washed with water (20 mL), brine, (20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude tan foam
  10. customPurification by flash column chromatography (100% dichloromethane to 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-a7fe1f1bdc4c4e30913a5dbc4435f05f
Source dataset
uspto-grants-2016_03
Patent number
US09290514B2

Reaction notes

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