ANILINE, p-CHLORO-N-METHYL-N-NITROSO- → 5-Chloro-1-methyl-3-phenylindole-2-acetic acid

HRID 583229

Reaction equation

HRID 583229 reaction equation
C([O:3][C:4](=[O:15])[CH2:5][C:6]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=O)C.C([O-])(=O)C.[Na+].Cl.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]([CH3:31])N)=[CH:25][CH:24]=1.ClC1C=CC(N(C)N=O)=CC=1>C(O)(=O)C.O.[Zn]>[Cl:22][C:23]1[CH:24]=[C:25]2[C:26](=[CH:27][CH:28]=1)[N:29]([CH3:31])[C:6]([CH2:5][C:4]([OH:3])=[O:15])=[C:8]2[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 13874ANILINE, p-CHLORO-N-METHYL-N-NITROSO-HCID 225855Ethyl 3-oxo-4-phenylbutanoateHCID 517045Sodium AcetateHCID 189874901-(4-Chlorophenyl)-1-methyl hydrazine hydrochloride

Product 1

HCID 154107305-Chloro-1-methyl-3-phenylindole-2-acetic acid

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent2×HCID 962WaterSolvent2×

Procedure

To a solution of γ-phenyl acetoacetic acid ethyl ester (2.88 g) in a mixture of acetic acid (30 ml) and water (10 ml) were added sodium acetate (1.83 g) and 1-(4-chlorophenyl)-1-methyl hydrazine hydrochloride (2.73 g) {prepared from 4-chloro-N-methyl-N-nitroso aniline by subjecting to reduction with zinc powder in a mixture of acetic acid and water [m.p.171-174° C.; NMR (200 MHz, DMSO-d6) ppm: 3.14(3H,s), 7.20(2H,d,J=9 Hz), 7.29(2H,d,J=9 Hz)]}. The mixture was stirred for 15 minutes at room temperature, then for 20 minutes at 110° C. The reaction mixture was concentrated, which was dissolved in ethyl acetate. The solution was washed with water, dilute hydrochloric acid, water, an aqueous solution of sodium hydrogencarbonate and water, successively, which was then dried, followed by distilling off the solvent. The residue was purified by means of a silica gel (30 g) column chromatography (hexane-ethyl acetate=4:1) to give ethyl ester of 5-chloro-1-methyl-3-phenylindole-2-acetic acid as an oily substance (4.34 g). [NMR (200 MHz, CDCl3) ppm: 1.29(3H,t,J=7 Hz), 3.76(3H,s), 3.86(2H,s), 4.24(2H,q,J=7 Hz), 7.17-7.62(8H,m)]

Workup

  1. waitfor 20 minutes at 110° C
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionwhich was dissolved in ethyl acetate
  4. washThe solution was washed with water, dilute hydrochloric acid, water
  5. dry with materialan aqueous solution of sodium hydrogencarbonate and water, successively, which was then dried
  6. distillationby distilling off the solvent
  7. customThe residue was purified by means of a silica gel (30 g) column chromatography (hexane-ethyl acetate=4:1)

Sources & evidence

ORD record
ord-7675e71e1f834be09d55c7bb12874277
Source dataset
uspto-grants-1999_07
Patent number
US05929107

Linked notes

Loading…