Methanol → 1-[(4-Chlorophenyl)methyl]-5-hydroxy-3-methyl-1H-indole-2-propanoic acid

HRID 1090194Notes

Reaction equation

HRID 1090194 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16]C)=[CH:13][CH:14]=3)[C:9]([CH3:18])=[C:8]2[CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[CH:4][CH:3]=1.B(Br)(Br)Br.CO>C(Cl)Cl>[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([OH:16])=[CH:13][CH:14]=3)[C:9]([CH3:18])=[C:8]2[CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromide2×HCID 15678781HCID 15678781, compound

Product 1

HCID 156787821-[(4-Chlorophenyl)methyl]-5-hydroxy-3-methyl-1H-indole-2-propanoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

Beginning with 3-[1-p-chlorobenzyl-5-methoxy-3-methylindol-2-yl]propionic acid which is described in J. Med. Chem., 1252 (1968), (2.7 g) was dissolved in 20 ml CH2Cl2 at 0° C. 7.6 ml BBr3 (1M in CH2Cl2) was added dropwise and the reaction stirred for 60 minutes. After 180 minutes at 23° C., another 4 ml BBr3 solution was added. The reaction was stirred for a further 180 minutes. The reaction was cooled to -20° C. and 15 ml MeOH added. The organic phase was washed with NaHCO3 (aqueous), dried with Na2SO4 and chromatographed on silica gel. Hydrolysis of the methyl ester was carried out as described in Example 2 to yield 2.2 g of the title compound.

Workup

  1. waitAfter 180 minutes at 23° C.
  2. stirringThe reaction was stirred for a further 180 minutes
  3. washThe organic phase was washed with NaHCO3 (aqueous)
  4. dry with materialdried with Na2SO4
  5. customchromatographed on silica gel
  6. customHydrolysis of the methyl ester

Sources & evidence

ORD record
ord-3b86d428877d4489b19d07d246489861
Source dataset
uspto-grants-1992_01
Patent number
US05081145

Reaction notes

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