Potassium Hydroxide → 3-(5-chloro-1H-indol-1-yl)propanoic acid

HRID 1876640Notes

Reaction equation

HRID 1876640 reaction equation
[OH-].[K+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2.Br[CH2:14][CH2:15][C:16]([O:18]C)=[O:17]>CS(C)=O.O>[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:14][CH2:15][C:16]([OH:18])=[O:17])[CH:8]=[CH:7]2

Participants

6

Reactant 3

HCID 14797Potassium Hydroxide2×HCID 76934Methyl 3-bromopropanoateHCID 871105-Chloroindole

Product 1

HCID 594664433-(5-chloro-1H-indol-1-yl)propanoic acidYield 68%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Under an N2 atmosphere, crushed KOH was added to a solution of 5-chloro-1H-indole (2.0 g, 13.2 mmol) in DMSO (19 mL, 0.7 M), and the mixture was stirred for 2 h at RT. Methyl 3-bromopropanoate (1.9 mL, 17.2 mmol) was added dropwise, and the reaction was continued to stir at RT overnight. After diluting with H2O, the reaction was cleared with a 4.5 N aqueous KOH solution and washed 3 times with CH2Cl2. The aqueous layer was acidified with a 2N HCl solution to pH 3 and extracted 3 times with CH2Cl2. The organic fractions were combined, dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-8% MeOH in CH2Cl2 gave 3-(5-chloro-1H-indol-1-yl)propanoic acid (2 g, 68%). 1H NMR (400 MHz, DMSO-d6) δ 7.58 (d, J=2.0 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.44 (d, J=3.1 Hz, 1H), 7.13 (dd, J=8.7, 2.1 Hz, 1H), 6.42 (dd, J=3.2, 0.7 Hz, 1H), 4.40 (t, J=6.8 Hz, 2H), 2.75 (t, J=6.8 Hz, 2H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=224.5; tR=2.74 min.

Workup

  1. stirringto stir at RT overnight
  2. washwashed 3 times with CH2Cl2
  3. extractionextracted 3 times with CH2Cl2
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-6c579ddf5e6949a0acf77f355856ffcb
Source dataset
uspto-grants-2012_11
Patent number
US08309587B2

Reaction notes

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