Triethylamine → 4-[[[(2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl]carbonyl]amino]benzeneacetamide

HRID 2076350Notes

Reaction equation

HRID 2076350 reaction equation
[CH:1]1([CH3:13])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([C:10]([OH:12])=O)[CH2:2]1.S(Cl)(Cl)=O.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]([NH2:28])=[O:27])=[CH:21][CH:20]=1.C(N(CC)CC)C>C(Cl)Cl>[NH2:28][C:26](=[O:27])[CH2:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:10]([CH:3]2[CH2:2][C@H:1]([CH3:13])[CH2:6][CH2:5][C@H:4]2[CH:7]([CH3:8])[CH3:9])=[O:12])=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 97896p-Menthane-3-carboxylic acidHCID 2380342-(4-Aminophenyl)acetamide

Product 1

HCID 670960184-[[[(2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexyl]carbonyl]amino]benzeneacetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The p-Menthane-3-carboxylic acid (obtained according to publication: Desmond Cunningham, Eva T. Gallagher, David H. Grayson, Patrick J. McArdle, Christina B. Storey, Deborah J. Wilcock; J. Chem. Soc., Perkin Trans. 1, 2002, 2692-2698), (2.5 g, 13.5 mmol) was heated under reflux with thionyl chloride (Alfa Aesar) (7 mL) for three hours. Then the excess of thionyl chloride was distilled off in vacuo. Residue was dissolved in CH2Cl2 (30 mL). This solution was added drop wise to the mixture of 4-aminophenylacetamide (2.2 g, 13.5 mmol) and triethylamine (1.8 g, 17.8 mmol) at 0° C. After ten minutes the solution was allowed to warm to room temperature. After 1 hour GC showed that reaction is completed. CH2Cl2 (50 mL) was added to the reaction and this mixture was washed by 0.1 N HCl aq, water, 0.1 N NaOH aq, by brine and dried over MgSO4. The mixture was then filtrated and evaporated give white solid which was crystallized from hot ethyl acetate providing 3 g (65%) product as white solid. C19H28N2O2 (MW 316.22); 1H NMR (500 MHz, DMSO-d6) δ: 9.79 (s, 1H), 7.51 (d, 2H, J=8.41), 7.36 (br s, 1H), 7.15 (d, 2H, J=8.41 Hz), 6.82 (br s, 1H), 3.30 (s, 2H), 2.30 (t, 1H, J=11.43 Hz of d, J=3.19 Hz), 1.70-1.77 (m, 2H), 1.61-1.68 (m, 2H), 1.51 (t, 1H, J=11.5 Hz, of t, J=2.8 Hz), 1.33-1.38 (brs, 1H), 1.17 (q, 1H, J=12.16 Hz), 1.02 (q, 1H, J=12.7 Hz, of d, J=2.7 Hz) 0.89-0.96 (m, 1H), 0.88 (d, 3H, J=6.5 Hz), 0.85 (d, 3H, J=6.9 Hz), 0.79 (d, 3H, J=6.9 Hz).

Workup

  1. distillationThen the excess of thionyl chloride was distilled off in vacuo
  2. dissolutionResidue was dissolved in CH2Cl2 (30 mL)
  3. additionThis solution was added drop
  4. waitAfter ten minutes the solution was allowed
  5. customAfter 1 hour GC showed that reaction
  6. washthis mixture was washed by 0.1 N HCl aq, water, 0.1 N NaOH aq, by brine
  7. dry with materialdried over MgSO4
  8. filtrationThe mixture was then filtrated
  9. customevaporated
  10. customgive white solid which
  11. customwas crystallized from hot ethyl acetate providing 3 g (65%) product as white solid

Sources & evidence

ORD record
ord-c277853349a44ba2a9e8cb548d4ee80e
Source dataset
uspto-grants-2011_04
Patent number
US07923577B2

Reaction notes

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