Dicyclohexylcarbodiimide → HCID 53665932, compound

HRID 1034193Notes

Reaction equation

HRID 1034193 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[C:16]1([C:22]2[CH2:23][C@H:24]([C:28](O)=O)[CH2:25][CH2:26][CH:27]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.O.OC1C2N=NNC=2C=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[Al+3].[Cl-].[Cl-].[OH-].[Na+]>ClCCl.O1CCCC1.CCOCC.O>[C:16]1([C:22]2[CH2:23][C@H:24]([CH2:28][N:40]3[CH2:41][CH2:42][N:37]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][N:31]=4)[CH2:38][CH2:39]3)[CH2:25][CH2:26][CH:27]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

12

Reactant 7

HCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 944591-(2-Pyridyl)piperazineHCID 6451240Aluminum(III) ChlorideHCID 10352816HCID 10352816, compoundHCID 21226445Aluminium lithium hydrideHCID 178526939HCID 178526939, compound

Product 1

HCID 53665932HCID 53665932, compoundYield 32.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Dicyclohexylcarbodiimide (0.506 g) in dichloromethane (10 mL) is added to (R)-3-phenyl-3-cyclohexenecarboxylic acid (0.414 g, Example D), 2-pyridylpiperazine (0.410 g) and hydroxybenzotriazole hydrate (0.332 g) in dichloromethane (40 mL) and stirred overnight. The mixture is filtered and evaporated. The residue is dissolved in ethyl acetate, filtered, washed with saturated sodium bicarbonate, 5% citric acid, 2N sodium carbonate, brine, dried over magnesium sulfate, filtered, and evaporated to leave a yellow solid. This solid is dissolved in tetrahydrofuran (5 mL) and added to lithium aluminum hydride (78 mg) in tetrahydrofuran (5 mL) pretreated with aluminum chloride (90 mg) in ether (5 mL) at 0° C. and stirred for 2 hours. Water (0.1 mL) and 25% sodium hydroxide (0.4 mL) are added and the mixture filtered, washed with brine, dried over magnesium sulfate, filtered, and evaporated to a yellow oil. This oil is purified by medium pressure liquid chromatography on silica gel eluting with 50% ethyl acetate in hexane to give 0.22 g of (R)-1-[(3-Phenyl-3-cyclohexen-1-yl)methyl]-4-(2-pyridinyl)piperazine as an off-white solid; mp 106°-108° C.

Workup

  1. filtrationThe mixture is filtered
  2. customevaporated
  3. dissolutionThe residue is dissolved in ethyl acetate
  4. filtrationfiltered
  5. washwashed with saturated sodium bicarbonate, 5% citric acid, 2N sodium carbonate, brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto leave a yellow solid
  10. stirringstirred for 2 hours
  11. filtrationthe mixture filtered
  12. washwashed with brine
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. customevaporated to a yellow oil
  16. customThis oil is purified by medium pressure liquid chromatography on silica gel eluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-edb6c1c058544f7086ae1a54eedb4a1b
Source dataset
uspto-grants-1994_05
Patent number
US05314896

Reaction notes

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