Diisopropylamine → Methyl 5-chloro-2-cyclohexyl-valerate

HRID 546696Notes

Reaction equation

HRID 546696 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH:13]1([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[Cl:24][CH2:25][CH2:26][CH2:27]I>C1COCC1.C(OCC)(=O)C.O>[Cl:24][CH2:25][CH2:26][CH2:27][CH:19]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:20]([O:22][CH3:23])=[O:21]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 813631-Chloro-3-iodopropaneHCID 139743Cyclohexaneacetic acid, methyl esterHCID 178418339Butyllithium

Product 1

HCID 66839252Methyl 5-chloro-2-cyclohexyl-valerate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (2.64 M solution in hexane, 3.8 ml) was added dropwise to a solution of diisopropylamine (1.55 ml) in THF (15 ml) under ice-cooling, and the reaction solution was stirred at the same temperature for 10 minutes. The reaction solution was cooled to −78° C. Then, a solution of methyl cyclohexylacetate (CAS No. 14352-61-5, 500 mg) in THF (3 ml) was added dropwise and the reaction solution was stirred at the same temperature for 30 minutes. Then, 1-chloro-3-iodopropane (CAS No. 6940-76-7, 1.1 ml) was added dropwise to the reaction solution. The reaction solution was stirred at the same temperature for 20 minutes and then gradually heated to room temperature. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was sequentially washed with 1 N hydrochloric acid, water, a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane-diethyl ether system) to obtain 1.00 g of the title compound. The property value of the compound is as follows.

Workup

  1. temperaturecooling
  2. stirringthe reaction solution was stirred at the same temperature for 30 minutes
  3. addition6940-76-7, 1.1 ml) was added dropwise to the reaction solution
  4. stirringThe reaction solution was stirred at the same temperature for 20 minutes
  5. temperaturegradually heated to room temperature
  6. customthe organic layer was separated
  7. washThe organic layer was sequentially washed with 1 N hydrochloric acid, water
  8. dry with materiala saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (elution solvent: hexane-diethyl ether system)

Sources & evidence

ORD record
ord-a263c540e4a04f208dfaf34a4fd53fa8
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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