1-Hydroxybenzotriazole → 1-[(2-Benzothienylcarbonyl)amino]cyclohexanecarboxylic acid phenylmethyl ester

HRID 73853

Reaction equation

HRID 73853 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[S:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[CH:15]=[C:14]1[C:22]([OH:24])=O.[C:25]1([CH2:31][O:32][C:33]([C:35]2([NH2:41])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)=[O:34])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[C:25]1([CH2:31][O:32][C:33]([C:35]2([NH:41][C:22]([C:14]3[S:13][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[CH:15]=3)=[O:24])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40]2)=[O:34])[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 95864Benzo(b)thiophene-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15176238Benzyl 1-aminocyclohexanecarboxylate

Product 1

HCID 576728971-[(2-Benzothienylcarbonyl)amino]cyclohexanecarboxylic acid phenylmethyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under ice-cooling, 5.9 g (31 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added to a solution of 5 g (28 mmol) of 2-benzothiophenecarboxylic acid, 6.5 g (28 mmol) of 1-aminocyclohexanecarboxylic acid phenylmethyl ester and 4.5 g (29 mmol) of 1-hydroxybenzotriazole in methylene chloride. After the mixture was stirred at room temperature overnight, the reaction solvent was distilled off under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate twice. The obtained organic layer was washed with a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium hydrogencarbonate solution and then saturated brine, and it was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, diethyl ether was added to the obtained residue, and the mixture was stirred overnight. The crystal was collected by filtration and heated/dried under reduced pressure to obtain 10 g (91%) of the title compound.

Workup

  1. temperatureUnder ice-cooling
  2. distillationthe reaction solvent was distilled off under reduced pressure
  3. additionWater was added to the residue
  4. extractionthe mixture was extracted with ethyl acetate twice
  5. washThe obtained organic layer was washed with a 10% aqueous potassium hydrogensulfate solution
  6. dry with materiala saturated aqueous sodium hydrogencarbonate solution and then saturated brine, and it was dried with anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure, diethyl ether
  8. additionwas added to the obtained residue
  9. stirringthe mixture was stirred overnight
  10. filtrationThe crystal was collected by filtration
  11. customheated/dried under reduced pressure

Sources & evidence

ORD record
ord-3f8e2bf61c354e568d0daf7c0bd00327
Source dataset
uspto-grants-2014_09
Patent number
US08829209B2

Linked notes

Loading…