1-Hydroxybenzotriazole → 1-[[[4-(Hydroxymethyl)phenyl]carbonyl]amino]cyclohexanecarboxylic acid phenylmethyl ester

HRID 448764Notes

Reaction equation

HRID 448764 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[OH:13][CH2:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=1.[C:24]1([CH2:30][O:31][C:32]([C:34]2([NH2:40])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)=[O:33])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[C:24]1([CH2:30][O:31][C:32]([C:34]2([NH:40][C:19]([C:18]3[CH:17]=[CH:16][C:15]([CH2:14][OH:13])=[CH:23][CH:22]=3)=[O:21])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]2)=[O:33])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 763604-(Hydroxymethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15176238Benzyl 1-aminocyclohexanecarboxylate

Product 1

HCID 576728131-[[[4-(Hydroxymethyl)phenyl]carbonyl]amino]cyclohexanecarboxylic acid phenylmethyl esterYield 56.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under ice-cooling, 6.94 g (36 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added to a solution of 5 g (33 mmol) of 4-(hydroxymethyl)benzoic acid, 7.7 g (33 mmol) of 1-aminocyclohexanecarboxylic acid phenylmethyl ester and 5.29 g (35 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 obtained residue was purified by silica gel column chromatography to obtain 6.83 g (56%) 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. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5d1ac4bc2ab44d33957f9d3ccb8ddd49
Source dataset
uspto-grants-2013_07
Patent number
US08481725B2

Reaction notes

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