Sodium Iodide → [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid ethyl ester

HRID 1516980Notes

Reaction equation

HRID 1516980 reaction equation
[I-].[Na+].[C:3](OC(=O)C)(=[O:5])[CH3:4].[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([S:17][C:18]2[C:26]3[C:25](=[N:27]O)[CH2:24][CH2:23][CH2:22][C:21]=3[N:20]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:19]=2[CH3:35])=[CH:13][CH:12]=1>C1(C)C(C)=CC=CC=1.C(O)(=O)C>[C:3]([NH:27][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:26]=1[C:18]([S:17][C:14]1[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=1)=[C:19]([CH3:35])[N:20]2[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])(=[O:5])[CH3:4]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 7918Acetic Anhydride2×HCID 76689533HCID 76689533, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 7237O-XyleneSolvent2×

Conditions

Temperature
97 °C

Procedure

In flask 1, a mixture of sodium iodide (171.6 mg, 1.14 mmol) in xylene (12.5 mL), acetic acid (12.5 ml) and acetic anhydride (4.2 mL, 44.54 mmoles) was heated to 97° C. In flask 2, acetic anhydride (4.2 mL, 44.5 mmol) was added to a stirred slurry of ethyl [3-(4-chlorophenylsulfanyl)-4-(hydroxyimino)-2-methyl-4,5,6,7-tetrahydro-1H-indol-1-yl]acetate (10 g, 22.3 mmol corrected for assay) in xylene (12.5 mL) and acetic acid (12.5 ml) at ambient temperature. The mixture in flask 2 was added to the mixture in flask 1 over 2-3 hours maintaining the temperature at 97° C. The reaction was held at this temperature for a further 2 hours following the end of the addition. The reaction was cooled to 60° C. and split into 2 equal size portions. One of these portions was cooled to r.t. and propan-1-ol (25 mL) was added, following by water (25 mL), added over 15 minutes, effecting a precipitation. After stirring for 1 h, the solid product was collected by filtration, washed with propan-1-ol (2×10 mL) and dried in vacuo at 40° C. to afford crude ethyl [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetate as a solid; 4.32 g (91% based on work up of half of the reaction mixture). Purity by HPLC 97.15 area %.

Workup

  1. additionThe mixture in flask 2 was added to the mixture in flask 1 over 2-3 hours
  2. temperaturemaintaining the temperature at 97° C
  3. additionthe end of the addition
  4. temperatureThe reaction was cooled to 60° C.
  5. customsplit into 2 equal size portions
  6. temperatureOne of these portions was cooled to r.t.
  7. additionpropan-1-ol (25 mL) was added
  8. additionadded over 15 minutes
  9. customa precipitation
  10. filtrationthe solid product was collected by filtration
  11. washwashed with propan-1-ol (2×10 mL)
  12. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-977e311a5f2d42eba3f30af90b93bab9
Source dataset
uspto-grants-2012_07
Patent number
US08227622B2

Reaction notes

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