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

HRID 1369667Notes

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.[CH3:20]I>C1COCC1>[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

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 MeI (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. 1 M 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

customremoved)
temperaturewarm to ambient temperature
stirringwith stirring for 15 hours
addition1 M Aq. HCl (50 mL) and EtOAc (250 mL) were added
customthe phases partitioned
washThe organic phase was washed with dilute NaHCO3 (1×100 mL), brine (1×100 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customthe residue purified by flash chromatography
washeluting with CH2Cl2/EtOAc (19:1 gradient to 15:1)

Sources & evidence

ORD record: ord-7388f2f9efb6404580cb055b2aae2d9c
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06579867B2

Reaction notes

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