HCID 11502325, compound → HCID 11595925, compound

HRID 505928Notes

Reaction equation

HRID 505928 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[N+:18]([O-])=O)[N:11]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:10]=2[CH3:27])=[CH:4][CH:3]=1.[H][H]>C(OCC)(=O)C.[Pt]>[NH2:18][C:16]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:17]=1[C:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[C:10]([CH3:27])[N:11]2[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

5

Reactant 2

HCID 11502325HCID 11502325, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 11595925HCID 11595925, compound

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of [3-(4-chlorophenylsulfanyl)-2-methyl-4-nitro-1H-indol-1-yl]acetic acid, ethyl ester (1.99 kg, 4.92 mol) in ethyl acetate (24.2 kg) was hydrogenated in the presence of a 1% Pt/C catalyst paste (1.39 kg 44% w/w) under 4 bar A hydrogen pressure. After 2 hours hydrogen uptake had ceased so the reaction mixture was inerted then filtered through Celite (2.60 kg). The solids were washed with ethyl acetate (3×8 kg) and the combined filtrates distilled until a volume of 26 L remained to leave a solution of [4-amino-3-(4-chlorophenylsulfanyl)-2-methylindol-1-yl]acetic acid, ethyl ester in ethyl acetate. This solution was cooled to 4° C. then triethylamine (0.50 kg, 4.94 mol) added, followed by an ethyl acetate line wash (0.82 kg). A solution of acetyl chloride (0.39 kg, 4.97 mol) in ethyl acetate (3 kg) was added followed by an ethyl acetate line wash (0.76 kg). The reaction mixture was heated at 40° C. for 17 hours then water (16.9 kg) added. The reaction mixture was distilled down until 24.6 kg of distillate had been removed then cooled to 20° C. The solid product was collected by filtration, washed with water (1.9 kg) followed by acetonitrile (1.6 kg) then dried in a vacuum oven at 40° C. to afford [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid, ethyl ester, 1.69 kg (82%) as an off white solid.

Workup

  1. filtrationwas inerted then filtered through Celite (2.60 kg)
  2. washThe solids were washed with ethyl acetate (3×8 kg)
  3. distillationthe combined filtrates distilled until a volume of 26 L

Sources & evidence

ORD record
ord-565d079b63514fe58f3749c1b89d8c80
Source dataset
uspto-grants-2010_08
Patent number
US07781598B2

Reaction notes

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