Hydrochloric Acid → 8-Hydroxymethyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one

HRID 871965Notes

Reaction equation

HRID 871965 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C[O:8][C:9]([C:11]1[C:12]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][CH3:31])=[CH:13][CH:14]=[C:15]2[C:20]=1[NH:19][C:18](=[O:21])[C:17]([CH3:23])([CH3:22])[NH:16]2)=O.Cl>O1CCCC1.O.C(OCC)(=O)C>[OH:8][CH2:9][C:11]1[C:12]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][CH3:31])=[CH:13][CH:14]=[C:15]2[C:20]=1[NH:19][C:18](=[O:21])[C:17]([CH3:22])([CH3:23])[NH:16]2

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 21226445Aluminium lithium hydrideHCID 247808448-Methoxycarbonyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one

Product 1

HCID 247808478-Hydroxymethyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-oneYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

Lithium aluminium hydride (26.0 mg, 0.64 mmol) was suspended in anhydrous tetrahydrofuran (0.5 mL) under nitrogen atmosphere. An anhydrous tetrahydrofuran solution (1.5 mL) of 8-methoxycarbonyl-7-(2-methoxyphenyl)-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 2-1, 108 mg, 0.32 mmol) was added thereto at 0° C., and stirred for 3 hours at the same temperature. After ethyl acetate (3 mL) and water (3 mL) were added dropwise successively, ethyl acetate (30 mL), water (30 mL) and 1N aqueous hydro chloride solution (5 mL) were added thereto, and the mixture was partitioned. After the water layer was extracted with ethyl acetate (20 mL), the organic layer was combined. The organic layer was washed with water (50 mL, 2 times) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (61.0 mg) as a pale yellow amorphous product. (Yield 61%)

Workup

  1. addition2-1, 108 mg, 0.32 mmol) was added
  2. customthe mixture was partitioned
  3. extractionAfter the water layer was extracted with ethyl acetate (20 mL)
  4. washThe organic layer was washed with water (50 mL, 2 times) and saturated brine (50 mL) successively
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-539fc1c8f197477a81ec0eecf4fb17a2
Source dataset
uspto-grants-2015_03
Patent number
US08975256B2

Reaction notes

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