Sodium hydride → methyl 9-(4-fluorobenzyl)-4-hydroxy-2-methyl-1-oxo-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate

HRID 1473255Notes

Reaction equation

[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([C:16]([O:18]C)=O)=[C:8]2[C:20](=[O:28])[N:21]([CH2:23][C:24]([O:26][CH3:27])=[O:25])[CH3:22])=[CH:4][CH:3]=1.[H-].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([OH:18])=[C:23]([C:24]([O:26][CH3:27])=[O:25])[N:21]([CH3:22])[C:20](=[O:28])[C:8]2=3)=[CH:29][CH:30]=1

Participants

Conditions

Temperature: 0 °C

Procedure

An ice cold solution of methyl 1-(4-fluorobenzyl)-2-((2-methoxy-2-oxoethyl)(methyl)carbamoyl)-1H-indole-3-carboxylate (3 g, 7.27 mmol) in N,N-Dimethylformamide (DMF) (36.4 ml) was treated with NaH (0.378 g, 9.46 mmol). After 1 h, the reaction mixture was cooled to 0° C. and slowly quenched with H2O. The mixture was extracted with EtOAc and the organic layer washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by ISCO (0-3% DCM/MeOH) to afford methyl 9-(4-fluorobenzyl)-4-hydroxy-2-methyl-1-oxo-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate (1.1 g, 2.89 mmol, 39.8% yield) as an orange solid. LCMS (m/z) ES+=381 (M+1).

Workup

customslowly quenched with H2O
extractionThe mixture was extracted with EtOAc
washthe organic layer washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by ISCO (0-3% DCM/MeOH)

Sources & evidence

ORD record: ord-0f51da11b51a4610a16ba6d74f7a2470
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012642B2

Reaction notes

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