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

HRID 277881Notes

Reaction equation

HRID 277881 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=5.8 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-ccab43306c364fb49908c2161071a462
Source dataset
uspto-grants-2002_03
Patent number
US06358948B1

Reaction notes

Loading…