Cyclopentylamine → N-cyclopentyl-2-mercapto-4-methoxybenzamide

HRID 404962Notes

Reaction equation

HRID 404962 reaction equation
C[Al](C)C.[CH:5]1([NH2:10])[CH2:9][CH2:8][CH2:7][CH2:6]1.[SH:11][C:12]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:13]=1[C:14](OC)=[O:15]>C(Cl)Cl>[CH:5]1([NH:10][C:14](=[O:15])[C:13]2[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[CH:21][C:12]=2[SH:11])[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 2906CyclopentylamineHCID 13769568Methyl 2-mercapto-4-methoxybenzoateHCID 16682925Trimethylaluminum

Product 1

HCID 50994688N-cyclopentyl-2-mercapto-4-methoxybenzamideYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

AlMe3 (10 mmol, 2.0 M in toluene) was added dropwise to a cooled (0° C.) suspension of cyclopentylamine (0.85 g, 10 mmol) in CH2Cl2 (30 mL). When the addition was complete, the reaction mixture was allowed to warm to room temperature and stirring was continued for 30 minutes until the gas evolution ceased. Then, a solution of methyl 2-mercapto-4-methoxy-benzoate (0.990 g, 5 mmol) was added. After stirring at 60° C. for 12 h, the mixture was cooled, and carefully quenched with 5% aq HCl (20 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3×15 mL). The combined organic extracts were washed with a saturated aqueous solution of NaHCO3 (15 mL) and brine. The organic phase was dried using MgSO4 and evaporated, filtered and the solvent was evaporated in vacuo. The resulting residue was purified by crystallization from Et2O to afford N-cyclopentyl-2-mercapto-4-methoxybenzamide as a tan solid (1.18 g, 94%). 1H NMR (DMSO-d6, 300 MHz): δ 8.26 (s, 1H), 7.51 (d, 1H, J=8.7 Hz), 7.01 (s, 1H), 6.72 (d, 1H, J=8. Hz), 5.62 (s, 1H), 4.16-4.14 (m, 1H), 3.78 (s, 3H), 1.99-1.80 (m, 2H), 1.79-1.68 (m, 2H), 1.66-1.53 (m, 4H). LC-MS (ESI) Calcd for C13H17NO2S [M+H]+: 252.09. Found: 251.95.

Workup

  1. temperaturea cooled
  2. additionWhen the addition
  3. stirringAfter stirring at 60° C. for 12 h
  4. temperaturethe mixture was cooled
  5. customcarefully quenched with 5% aq HCl (20 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with CH2Cl2 (3×15 mL)
  8. washThe combined organic extracts were washed with a saturated aqueous solution of NaHCO3 (15 mL) and brine
  9. customThe organic phase was dried
  10. customevaporated
  11. filtrationfiltered
  12. customthe solvent was evaporated in vacuo
  13. customThe resulting residue was purified by crystallization from Et2O

Sources & evidence

ORD record
ord-451eb942f8d4492583ad781ac36b8b15
Source dataset
uspto-grants-2014_06
Patent number
US08748632B2

Reaction notes

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