Cyclohexanone → HCID 68854288, compound

HRID 28839Notes

Reaction equation

HRID 28839 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1.C([Li])CCC.[C:27]1(=[O:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>O1CCCC1>[OH:33][C:27]1([CH:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:8][N:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 20294517HCID 20294517, compoundHCID 178418339Butyllithium

Product 1

HCID 68854288HCID 68854288, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of tert-butyl 4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylate (466 mg, 1.60 mmol) in dry tetrahydrofuran (6 mL) under nitrogen was cooled to −78° C. and treated dropwise with a solution of n-butyllithium (2.5 M in hexanes, 0.70 mL, 1.75 mmol). The resulting solution was stirred at −78° C. for 1 h. The reaction was then treated with a solution of cyclohexanone (174 mg, 1.77 mmol) in dry tetrahydrofuran (0.8 mL). The reaction was stirred at −78° C. for 45 min, after which time the reaction was then quenched by the addition of a saturated aqueous solution of sodium bicarbonate, and the tetrahydrofuran was removed in vacuo. The resulting residue was partitioned between water and ethyl acetate and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×30 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo and the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% methanol/EtOAc to 10% methanol/EtOAc) to yield 484 mg (78%) tert-butyl 4-[2-(1-hydroxy-cyclohexyl)-2-pyridin-2-yl-ethyl]-piperazine-1-carboxylate as a colorless oil.

Workup

  1. stirringThe reaction was stirred at −78° C. for 45 min
  2. customafter which time the reaction was then quenched by the addition of a saturated aqueous solution of sodium bicarbonate
  3. customthe tetrahydrofuran was removed in vacuo
  4. customThe resulting residue was partitioned between water and ethyl acetate
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  7. dry with materialthe combined organic extracts were dried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customthe product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% methanol/EtOAc to 10% methanol/EtOAc)

Sources & evidence

ORD record
ord-6946c7709a474ac0942045de99ad099d
Source dataset
uspto-grants-2008_09
Patent number
US07419980B2

Reaction notes

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