2-Cyclohepten-1-one → HCID 15643612, compound

HRID 654975

Reaction equation

HRID 654975 reaction equation
CN[C@@H:3]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:4]N1CCCCC1.C([Li])CCC.[C:22]1(=[O:29])CCCC[CH:24]=[CH:23]1>CCOCC.[Cu]I>[CH2:16]([C@H:11]1[CH2:3][CH2:4][CH2:24][CH2:23][C:22](=[O:29])[CH2:12]1)[CH2:15][CH2:14][CH3:13]

Participants

6

Reactant 3

HCID 707232-Cyclohepten-1-oneHCID 11117512HCID 11117512, compoundHCID 178418339Butyllithium2×

Product 1

HCID 15643612HCID 15643612, compoundYield 63.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-65 °C

Procedure

(S)-N-methyl-1-phenyl-2-(1-piperidinyl)ethanamine (348.4 mg, 1.60 mmol) was dissolved in ether (12 mL) and n-butyl lithium (2.5M in hexanes, 0.61 mL, 1.53 mmol) was added to the solution at -65° C. The solution was stirred for 5 min at -65° C., gradually (for 20 min) warmed to 0° C. and stirred for 10 min at 0° C. To a second flask was added CuI (254 mg, 1.33 mmol) and 10 mL of diethyl ether. This solution was cooled to -40° C. and treated with n-butyl lithium (0.51 mL, 1.28 mmol). The solution in the first flask was cooled to -35° C. and added via canula to the solution of n-BuCu in the second flask. The resulting solution was stirred for 15 min at -35° C., for 10 min at -30° C., and cooled to -78° C. After 30 min, 2-cycloheptenone (141 mg, 1.28 mmol) was added slowly at -78° C. The reaction mixture was quenched after 1 hr by adding 4N NH4Cl (15 mL) at -78° C. and extracted with ether (20 mL). The extract was washed with 1N HCl (15 mL), dried (Na2SO4) and concentrated. The oily residue was purified by column chromatography on silica gel (10:1=hexanes/ethyl acetate) to afford (S)-3-n-butylcycloheptanone (136 mg, 63% chemical yield, 96% ee, [α]D =-33.0 (c= 3.2, chloroform)).

Workup

  1. temperaturegradually (for 20 min) warmed to 0° C.
  2. stirringstirred for 10 min at 0° C
  3. temperatureThis solution was cooled to -40° C.
  4. temperatureThe solution in the first flask was cooled to -35° C.
  5. additionadded via canula to the solution of n-BuCu in the second flask
  6. stirringThe resulting solution was stirred for 15 min at -35° C., for 10 min at -30° C.
  7. temperaturecooled to -78° C
  8. waitAfter 30 min
  9. customThe reaction mixture was quenched after 1 hr
  10. additionby adding 4N NH4Cl (15 mL) at -78° C.
  11. extractionextracted with ether (20 mL)
  12. washThe extract was washed with 1N HCl (15 mL)
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated
  15. customThe oily residue was purified by column chromatography on silica gel (10:1=hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-9e64563bec07459890a0f68d8023c2d3
Source dataset
uspto-grants-1992_07
Patent number
US05134238

Linked notes

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