3-Bromopropionic acid → 3-[2-bromo-3-cyclohexyl-6-(methoxycarbonyl)-1H-indol-1-yl]propanoic acid

HRID 1714069Notes

Reaction equation

HRID 1714069 reaction equation
[H-].[Na+].[Br:3][C:4]1[NH:5][C:6]2[C:11]([C:12]=1[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[CH:10][CH:9]=[C:8]([C:19]([O:21][CH3:22])=[O:20])[CH:7]=2.N1C2C(=C[CH:28]=[C:29]([C:32]([O:34]C)=[O:33])C=2)C=C1.BrCCC(O)=O>CN(C=O)C>[Br:3][C:4]1[N:5]([CH2:28][CH2:29][C:32]([OH:34])=[O:33])[C:6]2[C:11]([C:12]=1[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[CH:10][CH:9]=[C:8]([C:19]([O:21][CH3:22])=[O:20])[CH:7]=2

Participants

6

Reactant 4

HCID 115533-Bromopropionic acidHCID 24758Sodium hydrideHCID 639844Methyl indole-6-carboxylateHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 685061433-[2-bromo-3-cyclohexyl-6-(methoxycarbonyl)-1H-indol-1-yl]propanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (3.5 eq, 60% dispersion in mineral oil) was added to a solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as described in WO 2004065367, from commercially available methyl indole-6-carboxylate) in DMF (0.2 M) and the solution allowed to stir at RT for 1 h. Then 3-bromopropanoic acid (1.1 eq) was added and the mixture stirred at RT for 2 h. DMF was concentrated in vacuo and the residue taken up in EtOAc. The organic phase was washed with 1 N HCl and then brine before being dried (Na2SO4), filtered and the solvent evaporated in vacuo. The title compound was used crude in the next step; MS (ES+) m/z 408 (M+H)+, m/z 410 (M+H)+.

Workup

  1. customprepared
  2. stirringthe mixture stirred at RT for 2 h
  3. concentrationDMF was concentrated in vacuo
  4. washThe organic phase was washed with 1 N HCl
  5. dry with materialbrine before being dried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-11ca5de60f7b48ee9e99cd8be230424c
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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