Hydrogen Peroxide → 3-(Cyclohexylmethoxy)-5-(methylsulfanyl)-1,2-thiazole-4-carboxamide

HRID 1178696Notes

Reaction equation

HRID 1178696 reaction equation
[CH:1]1([CH2:7][O:8][C:9]2[C:13]([C:14]#[N:15])=[C:12]([S:16][CH3:17])[S:11][N:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:18]O.O>S(=O)(=O)(O)O.C(O)(=O)C.C(OC(=O)C)(=O)C>[CH:1]1([CH2:7][O:8][C:9]2[C:13]([C:14]([NH2:15])=[O:18])=[C:12]([S:16][CH3:17])[S:11][N:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 3

HCID 784Hydrogen Peroxide2×HCID 962WaterHCID 695160083-(Cyclohexylmethoxy)-5-(methylsulfanyl)-1,2-thiazole-4-carbonitrile

Product 1

HCID 695154003-(Cyclohexylmethoxy)-5-(methylsulfanyl)-1,2-thiazole-4-carboxamideYield 62%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 1118Sulfuric AcidSolventHCID 7918Acetic AnhydrideSolvent

Procedure

3-Cyclohexylmethoxy-5-methylsulfanyl-isothiazole-4-carbonitrile (3) (6.3 g, 23.5 mmol) is dissolved in conc. sulfuric acid (31.5 mL) and stirred at room temperature for 24 hrs. Ice was added and the resulting suspension was filtered and washed with water and then washed with 1N NaOH. The solids were dried in vacuo to obtain crude 3-cyclohexylmethoxy-5-methylsulfanyl-isothiazole-4-carboxylic acid amide (4, 8.7 g). This solid is slurried in acetic acid (37 mL) and acetic anhydride (37 mL). Hydrogen peroxide (30%, 18.5 mL) is then added and the reaction is stirred at room temperature for 18 hours. More hydrogen peroxide (30%, 18.5 mL) is then added and the reaction is stirred at room temperature for 3 days. Water is then added and the suspension is filtered and the solids are further dried in vacuo to provide 5 (5.06 g, 62%). 1H NMR (d6 DMSO): δ 7.97 (1H, s), 7.87 (1H, s), 4.14 (2H, d, J=6.0 Hz), 3.54 (3H, s), 1.59–1.78 (6H, m), 1.09–1.25 (3H, m), 0.94–1.03 (2H, m); LRMS (M+): 318.9.

Workup

  1. additionIce was added
  2. filtrationthe resulting suspension was filtered
  3. washwashed with water
  4. washwashed with 1N NaOH
  5. customThe solids were dried in vacuo
  6. customto obtain crude 3-cyclohexylmethoxy-5-methylsulfanyl-isothiazole-4-carboxylic acid amide (4, 8.7 g)
  7. stirringthe reaction is stirred at room temperature for 18 hours
  8. stirringthe reaction is stirred at room temperature for 3 days
  9. filtrationthe suspension is filtered
  10. customthe solids are further dried in vacuo

Sources & evidence

ORD record
ord-97047990b62446dfba69ba2b0d205cb3
Source dataset
uspto-grants-2007_10
Patent number
US07276602B2

Reaction notes

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