Sodium hydride → HCID 50994682, compound

HRID 1669471Notes

Reaction equation

HRID 1669471 reaction equation
[H-].[Na+].[CH:3]1([C:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][CH:16]=3)[NH:11][C:10]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[OH:28])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:30][C:31]1([CH2:39]Br)[CH2:36][O:35][C:34]([CH3:38])([CH3:37])[O:33][CH2:32]1>CN(C=O)C>[CH:3]1([C:9]2[C:17]3[CH:16]=[CH:15][C:14]([C:18]([O:20][CH3:21])=[O:19])=[CH:13][C:12]=3[N:11]3[C:10]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[O:28][CH2:39][C:31]2([CH2:36][O:35][C:34]([CH3:38])([CH3:37])[O:33][CH2:32]2)[CH2:30]3)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11995228Methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylateHCID 145372285,5-Bis(bromomethyl)-2,2-dimethyl-1,3-dioxane

Product 1

HCID 50994682HCID 50994682, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

NaH (5 eq, 60% dispersion in mineral oil) was added to a degassed solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as described in published International patent application WO2006/046030) in DMF (0.2 M) and the solution was allowed to stir for 20 min at RT. The mixture was then placed in an oil bath preheated at 70° C., a degassed solution of 5,5-bis(bromomethyl)-2,2-dimethyl-1,3-dioxane (1.5 eq) in dry DMF (0.4M) was added and the mixture was stirred for 1 h; additional electrophile (1.5 eq) was added and stirring was continued for 3 h at 70° C. The reaction was quenched with sat. aq. NH4Cl, acidified with 1N HCl and extracted with Et2O; the organic layer was washed with H2O and brine, dried over Na2SO4 and the solvent was removed in vacuo. The crude was purified by FC (PE/EtOAc) to afford the title compound (50%) and recovered starting material (44%). (ES+) m/z 490 (M+H)+.

Workup

  1. customThe mixture was then placed in an oil bath
  2. custompreheated at 70° C.
  3. stirringthe mixture was stirred for 1 h
  4. additionadditional electrophile (1.5 eq) was added
  5. stirringstirring
  6. waitwas continued for 3 h at 70° C
  7. customThe reaction was quenched with sat. aq. NH4Cl
  8. extractionextracted with Et2O
  9. washthe organic layer was washed with H2O and brine
  10. dry with materialdried over Na2SO4
  11. customthe solvent was removed in vacuo
  12. customThe crude was purified by FC (PE/EtOAc)

Sources & evidence

ORD record
ord-f26f06bbe0f34065886be2203a5d906d
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

Loading…