Sodium hydride → HCID 66674541, compound

HRID 1714025Notes

Reaction equation

[Br:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[H-].[Na+].[CH3:23][O:24][CH:25]([O:28][CH3:29])[CH2:26]Br>CN(C=O)C>[Br:1][C:2]1[N:3]([CH2:26][CH:25]([O:28][CH3:29])[O:24][CH3:23])[C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as described in published International patent application WO2004/087714) (0.2 M, 1 eq.) in DMF at RT was added NaH (60% dispersion in mineral oil, 1.75 eq). After 1 h, KI (8 mol %) and bromoacetaldehyde dimethyl acetal (2.5 eq) were added and the reaction heated at 80° C. for 17 h. After cooling to RT, the reaction was quenched by addition of aqueous HCl (1N) and extracted into EtOAc (×3). The combined organics were washed with HCl (1N), H2O and brine before being dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash column chromatography (Biotage, 5-10% EtOAc/PE gradient) gave the title compound as a white solid (79%); MS (ES+) m/z 446 (M+H)+, 448 (M+H)+.

Workup

temperatureAfter cooling to RT
customthe reaction was quenched by addition of aqueous HCl (1N)
extractionextracted into EtOAc (×3)
washThe combined organics were washed with HCl (1N), H2O and brine
dry with materialbefore being dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by flash column chromatography (Biotage, 5-10% EtOAc/PE gradient)

Sources & evidence

ORD record: ord-5049ce29f07b47b0b2467305744fcd71
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795247B2

Reaction notes

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