Sodium Iodide → (4-acetylamino-2-methyl-1H-indol-1-yl)acetic acid

HRID 1516990Notes

Reaction equation

HRID 1516990 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].O[N:9]=[C:10]1[CH2:18][CH2:17][CH2:16][C:15]2[N:14]([CH2:19][C:20]([OH:22])=[O:21])[C:13]([CH3:23])=[CH:12][C:11]1=2.[I-].[Na+]>C(O)(=O)C.C1(C)C(C)=CC=CC=1>[C:1]([NH:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[C:13]([CH3:23])[N:14]2[CH2:19][C:20]([OH:22])=[O:21])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 7918Acetic Anhydride2×HCID 76689531HCID 76689531, compound

Product 1

HCID 45118128(4-acetylamino-2-methyl-1H-indol-1-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 7237O-XyleneSolvent2×

Conditions

Temperature
95 °C

Procedure

Acetic anhydride (1.0 mL, 10.6 mmol) was added to a stirred slurry of 2-[4-(hydroxyimino)-2-methyl-4,5,6,7-tetrahydro-1H-indol-1-yl]acetic acid (2.0 g, 9.0 mmol) in a mixture of acetic acid (10 mL) and xylene (10 mL) at r.t. in reaction flask 1 (mildly exothermic addition) then the mixture was held with stirring for 75 mins. Meanwhile, reaction flask 2 was charged with acetic acid (5 mL), xylene (5 mL), acetic anhydride (2.6 mL, 27.5 mmol), and sodium iodide (270 mg, 1.80 mmol) and the mixture was heated to 90-100° C. with stirring. The contents of reaction flask 1 were transferred to reaction flask 2 in aliquots over a period of 1.5 h, whilst maintaining the reaction temperature at 90-100° C. Reaction flask 1 was rinsed with a mixture of xylene (2 mL) and acetic acid (2 mL) which was transferred into reaction flask 2. Subsequently, the reaction mixture was maintained at 100° C. for a further 2.5 h and was then allowed to cool to r.t. The liquid phase was decanted off from a thick residue in the reaction flask and the residue was washed with acetic acid (5 mL) followed by xylene (5 mL). The decanted liquid and washes were combined and evaporated to dryness in vacuo to leave a dark brown residue. Analysis by HPLC and LC-MS showed 29.2 area % of a peak giving m/z 247 (MH+).

Workup

  1. additionmildly exothermic addition) then the mixture
  2. customMeanwhile, reaction flask 2
  3. stirringwith stirring
  4. customThe contents of reaction flask 1
  5. customwere transferred to reaction flask 2 in aliquots over a period of 1.5 h
  6. temperaturewhilst maintaining the reaction temperature at 90-100° C
  7. customReaction flask 1
  8. washwas rinsed with a mixture of xylene (2 mL) and acetic acid (2 mL) which
  9. customwas transferred into reaction flask 2
  10. temperatureSubsequently, the reaction mixture was maintained at 100° C. for a further 2.5 h
  11. temperatureto cool to r.t
  12. customThe liquid phase was decanted off from a thick residue in the reaction flask
  13. washthe residue was washed with acetic acid (5 mL)
  14. customevaporated to dryness in vacuo
  15. customto leave a dark brown residue
  16. customgiving m/z 247 (MH+)

Sources & evidence

ORD record
ord-b10b9ac91d6f4073af05bb74467c3065
Source dataset
uspto-grants-2012_07
Patent number
US08227622B2

Reaction notes

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