Sodium hydride → 6-Bromo-1-(4-methoxy-benzyl)-4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one

HRID 2120755Notes

Reaction equation

HRID 2120755 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][C:5]2([CH3:14])[CH3:13].[H-].[Na+].[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Cl)=[CH:21][CH:20]=1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:23][C:22]1[CH:25]=[CH:26][C:19]([O:18][CH3:17])=[CH:20][CH:21]=1)[C:7](=[O:12])[CH2:6][C:5]2([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 107295896-bromo-4,4-dimethyl-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 234355916-Bromo-1-(4-methoxy-benzyl)-4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-bromo-4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one (0.5 g, 1.97 mmol) in THF (25 mL) was added 60% NaH (0.12 g, 2.95 mmol) suspended in mineral oil. The resulting reaction mixture was stirred at room temperature for 30 min., 4-methoxybenzyl chloride (0.34 g, 2.17) added, and heated under reflux for 20 h. The reaction was cooled to room temperature then quenched slowly with water. After extraction with ethyl acetate, the organic layer was dried (MgSO4), evaporated and the residue purified by chromatography (SiO2 3:7 ethyl acetate/hexane). The white crystalline product was obtained (0.35 g, 48%); mp 118-119° C., 1H NMR (DMSO-d6) δ 1.23 (s, 6H), 2.59 (s, 2H), 3.70 (s, 3H), 3.72 (s, 1H), 4.41 (d, 1H, J=5.86 Hz), 5.09 (s, 1H), 6.87 (m, 2H), 7.01 (d, 1H, J=8.78 Hz), 7.17 (d, 1H, J=8.98 Hz), 7.23 (d, 1H, J=8.79), 7.34 (dd, 1H, J=6.59 and 2.2 Hz), 7.43(d, 1H, J=2.2 Hz); MS (APCI (+)) [M+H]+=374/376.

Workup

  1. customThe resulting reaction mixture
  2. temperatureheated
  3. temperatureunder reflux for 20 h
  4. temperatureThe reaction was cooled to room temperature
  5. customthen quenched slowly with water
  6. extractionAfter extraction with ethyl acetate
  7. dry with materialthe organic layer was dried (MgSO4)
  8. customevaporated
  9. customthe residue purified by chromatography (SiO2 3:7 ethyl acetate/hexane)
  10. customThe white crystalline product was obtained (0.35 g, 48%)

Sources & evidence

ORD record
ord-394284d1e9e94286b03ce2b829aa2b08
Source dataset
uspto-grants-2004_02
Patent number
US06693103B2

Reaction notes

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