4-Methylmorpholine → 8-Methoxy-2-[4-(phenylaminocarbonyl-amino)piperidylcarbonyl]-chroman

HRID 2396476Notes

Reaction equation

HRID 2396476 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][CH:10]([C:13]([OH:15])=O)[CH2:9][CH2:8]2.[OH:16]N1C2C=CC=CC=2N=N1.[CH:26]1([N:32]=[C:33]=[N:34][CH:35]2CCCCC2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.C[N:42]1[CH2:47][CH2:46]O[CH2:44][CH2:43]1>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][CH:10]([C:13]([N:42]1[CH2:43][CH2:44][CH:35]([NH:34][C:33]([NH:32][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:16])[CH2:46][CH2:47]1)=[O:15])[CH2:9][CH2:8]2

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 152291968-Methoxychroman-2-carboxylic acid

Product 1

HCID 152291958-Methoxy-2-[4-(phenylaminocarbonyl-amino)piperidylcarbonyl]-chromanYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution, cooled to 0° C., of 770 mg (3.51 mmol) of 8-methoxychromancarboxylic acid and 586 mg (3.83 mmol) of 1-hydroxybenzotriazole in 20 ml of anhydrous dichloromethane is treated with 723 mg (3.51 mmol) of dicyclohexylcarbodiimide and stirred for 5 min. A solution of 700 mg (3.19 mmol) of the compound from Example II and 0.88 ml (8.00 mmol) of N-methylmorpholine in 20 ml of dichloromethane is then added dropwise, and the reaction mixture may be stirred at room temperature for 1 h. The resultant urea is then removed by filtration, the filtrate is concentrated in vacuo and the crude product is purified by chromatography on 150 g of silica gel (dichloromethane/methanol 95:5). The product-containing fractions are collected, the solvent is evaporated in vacuo, and the residue is triturated with diethyl ether, filtered off with suction and dried in a high vacuum. 1.24 g (95%) of the title compound are obtained as colourless crystals.

Workup

  1. stirringthe reaction mixture may be stirred at room temperature for 1 h
  2. customThe resultant urea is then removed by filtration
  3. concentrationthe filtrate is concentrated in vacuo
  4. customthe crude product is purified by chromatography on 150 g of silica gel (dichloromethane/methanol 95:5)
  5. customThe product-containing fractions are collected
  6. customthe solvent is evaporated in vacuo
  7. customthe residue is triturated with diethyl ether
  8. filtrationfiltered off with suction
  9. customdried in a high vacuum

Sources & evidence

ORD record
ord-2307967cf0994d6686fd81f26008b0f0
Source dataset
uspto-grants-1996_02
Patent number
US05492918

Reaction notes

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