Tetrahydrofuran → 1-Methyl-4-phenyl-3,4-dihydrocarbostyril

HRID 1841002Notes

Reaction equation

HRID 1841002 reaction equation
[H-].[Na+].[C:3]1([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][C:11](=[O:19])[CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:20]1COCC1>>[CH3:20][N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:10][C:11]1=[O:19]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 2725094-Phenyl-3,4-dihydroquinolin-2(1h)-one

Product 1

HCID 121015481-Methyl-4-phenyl-3,4-dihydrocarbostyril

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (1.2 eq., 0.537 g of 60% dispersion in mineral oil) in THF (50 mL) under N2 at 0° C. was added the product from Step A (1.0 eq., 2.50 g) in THF (50 mL) via cannula over a period of 5 minutes. The resulting pale yellow mixture was stirred at 0° C. for 10 minutes, then Mel (2.0 eq., 1.39 mL) was added. The opaque yellow mixture was allowed to slowly (ice bath not removed) warm to ambient temperature with stirring for 15 hours. 1M Aq. HCl (50 mL) and EtOAc (250 mL) were added and the phases partitioned. The organic phase was washed with dilute NaHCO3 (1×100 mL), brine (1×100 mL), then dried over MgSO4, filtered, concentrated, and the residue purified by flash chromatography eluting with CH2Cl2/EtOAc (19:1 gradient to 15:1) to provide 1-methyl-4-phenyl-3,4-dihydrocarbostyril.

Workup

  1. additionMel (2.0 eq., 1.39 mL) was added
  2. customremoved)
  3. temperaturewarm to ambient temperature
  4. stirringwith stirring for 15 hours
  5. addition1M Aq. HCl (50 mL) and EtOAc (250 mL) were added
  6. customthe phases partitioned
  7. washThe organic phase was washed with dilute NaHCO3 (1×100 mL), brine (1×100 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customthe residue purified by flash chromatography
  12. washeluting with CH2Cl2/EtOAc (19:1 gradient to 15:1)

Sources & evidence

ORD record
ord-3711b1b115084de692683a17b57a431c
Source dataset
uspto-grants-2004_01
Patent number
US06683075B1

Reaction notes

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