Chloromethyl Methyl Ether → HCID 9924028, compound

HRID 1634970Notes

Reaction equation

HRID 1634970 reaction equation
[CH3:1][C:2]1([CH3:22])[O:7][C:6](=[O:8])[NH:5][C:4]2[CH:9]=[CH:10][C:11]([C:13]3[CH:14]=[C:15]([CH:18]=[C:19]([F:21])[CH:20]=3)[C:16]#[N:17])=[CH:12][C:3]1=2.[H-].[Na+].Cl[CH2:26][O:27][CH3:28]>CN(C=O)C>[F:21][C:19]1[CH:18]=[C:15]([CH:14]=[C:13]([C:11]2[CH:10]=[CH:9][C:4]3[N:5]([CH2:26][O:27][CH3:28])[C:6](=[O:8])[O:7][C:2]([CH3:22])([CH3:1])[C:3]=3[CH:12]=2)[CH:20]=1)[C:16]#[N:17]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 98391343-(4,4-dimethyl-2-oxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-5-fluorobenzonitrile

Product 1

HCID 9924028HCID 9924028, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-fluorobenzonitrile (0.150 g, 0.51 mmol) in DMF (5 mL) was treated at rt with sodium hydride (0.061 g, 1.53 mmol). The mixture was stirred for 30 minutes and treated with chloromethyl methylether (0.062 g, 7.7 mmol). Upon completion of the reaction, the reaction mixture was quenched with water (25 mL) and extracted with ethyl acetate (3×30 mL), dried over MgSO4, and concentrated. The residue was purified via chromatography (silica gel, 25% ethyl acetate/hexane) to give 3-fluoro-5-(1-methoxymethyl-4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)benzonitrile as a white solid (0.11 g, 65%): mp 169-171° C; 1H-NMR (DMSO-d6) δ8.17 (bs, 1H), 8.03 (dt, 1H, J=10.4, 2.13 Hz), 7.85-7.77 (m, 3H), 7.31 (d, 1H, J=8.49 Hz), 5.33 (s, 2H), 3.35 (s, 3H), 1.7 (s, 6H); MS (APCI) m/z 341 ([M+H]+], 50%); Anal. Calc. For C19H17FN2O3: C, 65.32, H, 5.19, N, 8.02. Found: C, 64.92, H, 4.96, N, 7.73.

Workup

  1. customUpon completion of the reaction
  2. customthe reaction mixture was quenched with water (25 mL)
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified via chromatography (silica gel, 25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9d1b471e1d5840f9aee0c971b117c247
Source dataset
uspto-grants-2003_01
Patent number
US06509334B1

Reaction notes

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