Sodium Hydroxide → Azd-1981

HRID 505929Notes

Reaction equation

HRID 505929 reaction equation
[OH-].[Na+].[C:3]([NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9]([S:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)=[C:10]([CH3:22])[N:11]2[CH2:16][C:17]([O:19]CC)=[O:18])(=[O:5])[CH3:4]>C(O)CC>[C:3]([NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9]([S:23][C:24]1[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=1)=[C:10]([CH3:22])[N:11]2[CH2:16][C:17]([OH:19])=[O:18])(=[O:5])[CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 11546184[4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid ethyl ester

Product 1

HCID 11292191Azd-1981

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
68 °C

Procedure

Aqueous sodium hydroxide (1 M, 11.7 kg) was added to a solution of [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid, ethyl ester (2.20 kg, 5.28 mol) in 1-propanol (8.2 kg) and the mixture heated to 68° C. After cooling to 40° C., the solution was filtered, the filter rinsed with water (1 kg) then methyl isobutyl ketone (17.8 kg) was added to the filtrate, which was re-heated to 80° C. Aqueous hydrochloric acid (1 M, 12.2 kg) was added over a period of 90 minutes then the mixture cooled to 19° C. The crystalline solid was collected by filtration, washed with water (2×4 kg), ethyl acetate (6 kg) then dried in a vacuum oven at 40° C. to provide [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid as white crystals, 1.87 kg (91%).

Workup

  1. temperatureAfter cooling to 40° C.
  2. filtrationthe solution was filtered
  3. washthe filter rinsed with water (1 kg)
  4. additionmethyl isobutyl ketone (17.8 kg) was added to the filtrate, which
  5. temperaturewas re-heated to 80° C
  6. additionAqueous hydrochloric acid (1 M, 12.2 kg) was added over a period of 90 minutes
  7. temperaturethe mixture cooled to 19° C
  8. filtrationThe crystalline solid was collected by filtration
  9. washwashed with water (2×4 kg), ethyl acetate (6 kg)
  10. customthen dried in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-8e16b0e5b2704f388e1de02580d63da6
Source dataset
uspto-grants-2010_08
Patent number
US07781598B2

Reaction notes

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