Diisopropylethylamine → 1-benzyl-4-[(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]piperidin-4-ol

HRID 2383014Notes

Reaction equation

HRID 2383014 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([OH:17])([C:14]([OH:16])=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.Cl.[CH:28]1([CH:34]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:37][CH2:36][NH:35]2)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>CN(C=O)C>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]([C:14]([N:35]2[CH2:36][CH2:37][C:38]3[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH:34]2[CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[O:16])([OH:17])[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 203941814-Piperidinecarboxylicacid, 4-hydroxy-1-(phenylmethyl)-HCID 675358401-Cyclohexyl-1,2,3,4-tetrahydroisoquinoline hydrochloride

Product 1

HCID 593965611-benzyl-4-[(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]piperidin-4-olYield 6.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-benzyl-4-hydroxypiperidine-4-carboxylic acid (951 mg) was dissolved in DMF (25 mL), and N,N′-carbonyldiimidazole (720 mg) was added thereto, followed by stirring at room temperature for 18 hours. Thereafter, N,N-diisopropylethylamine (784 mg) and 1-cyclohexyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (1.22 g) were added to the reaction liquid, followed by stirring at 60° C. for 18 hours. The solvent was evaporated, and water and EtOAc were added to the reaction liquid. The resulting insoluble materials were separated through celite, extracted with EtOAc and dried over magnesium sulfate, and the solvent was evaporated. The resulting residue was purified by silica gel column chromatography (chloroform-MeOH) and dissolved in 1,4-dioxane (12 mL), and di-tert-butyl dicarbonate (1.3 g) was added thereto, followed by stirring at room temperature for 1 hour. The solvent was evaporated and the resulting residue was purified by silica gel column chromatography (hexane-EtOAc and then chloroform-MeOH) to obtain 1-benzyl-4-[(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]piperidin-4-ol (115 mg).

Workup

  1. stirringby stirring at 60° C. for 18 hours
  2. customThe solvent was evaporated
  3. additionwater and EtOAc were added to the reaction liquid
  4. customThe resulting insoluble materials were separated through celite
  5. extractionextracted with EtOAc
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent was evaporated
  8. customThe resulting residue was purified by silica gel column chromatography (chloroform-MeOH)
  9. dissolutiondissolved in 1,4-dioxane (12 mL)
  10. additiondi-tert-butyl dicarbonate (1.3 g) was added
  11. stirringby stirring at room temperature for 1 hour
  12. customThe solvent was evaporated
  13. customthe resulting residue was purified by silica gel column chromatography (hexane-EtOAc

Sources & evidence

ORD record
ord-42d4f0b31aa6401195e5d11b4b4bb99e
Source dataset
uspto-grants-2012_09
Patent number
US08263607B2

Reaction notes

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