Hydrochloric Acid → 1-(4-(1-(Methoxycarbonyl)cyclopropyl)benzyl)-2,3-dimethyl-1H-indole-5-carboxylic acid

HRID 2170621Notes

Reaction equation

HRID 2170621 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH3:11])=[CH:8][C:7]([C:12]([OH:14])=[O:13])=[CH:6][CH:5]=2.Br[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([C:26]([O:28][CH3:29])=[O:27])[CH2:25][CH2:24]2)=[CH:19][CH:18]=1.[H-].[Na+].Cl>CN(C=O)C.C(OCC)(=O)C>[CH3:29][O:28][C:26]([C:23]1([C:20]2[CH:19]=[CH:18][C:17]([CH2:16][N:3]3[C:4]4[C:9](=[CH:8][C:7]([C:12]([OH:14])=[O:13])=[CH:6][CH:5]=4)[C:10]([CH3:11])=[C:2]3[CH3:1])=[CH:22][CH:21]=2)[CH2:25][CH2:24]1)=[O:27]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydride2×HCID 6933862,3-Dimethyl-1H-indole-5-carboxylic acidHCID 57443306Methyl 1-(4-(bromomethyl)phenyl)cyclopropanecarboxylate

Product 1

HCID 710757301-(4-(1-(Methoxycarbonyl)cyclopropyl)benzyl)-2,3-dimethyl-1H-indole-5-carboxylic acidYield 41.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,3-dimethyl-1H-indole-5-carboxylic acid (500 mg, 2.3 mmol) in anhydrous DMF (20 mL) was added methyl 1-(4-(bromomethyl)phenyl)cyclopropanecarboxylate (620 mg) followed by NaH (230 mg). The resulting solution was allowed to stir overnight under argon atmosphere. The remaining NaH was hydrolyzed by the careful addition of a 0.5 N HCl solution. The mixture was diluted with ethyl acetate, washed with a 0.5 N HCl solution and brine, dried on MgSO4, and concentrated. The crude residue was purified by chromatography on silica gel (Hexane/Ethyl acetate 5/5) to afford an orange powder (361 mg). ESI-MS (m/z): 378 [MH]+

Workup

  1. washwashed with a 0.5 N HCl solution and brine
  2. customdried on MgSO4
  3. concentrationconcentrated
  4. customThe crude residue was purified by chromatography on silica gel (Hexane/Ethyl acetate 5/5)

Sources & evidence

ORD record
ord-81acfb81aff3430eaa6a76c78354052e
Source dataset
uspto-grants-2015_06
Patent number
US09051265B2

Reaction notes

Loading…