Diisopropylamine → HCID 66839456, compound

HRID 546718Notes

Reaction equation

HRID 546718 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][C:14]1([CH3:25])[O:19][CH:18]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:17][CH2:16][CH2:15]1.[Cl:26][CH2:27][CH2:28][CH2:29]I.[Cl-].[NH4+]>C1COCC1.O.C(OCC)(=O)C.CN(C)P(N(C)C)(N(C)C)=O>[Cl:26][CH2:27][CH2:28][CH2:29][CH:20]([CH:18]1[CH2:17][CH2:16][CH2:15][C:14]([CH3:25])([CH3:13])[O:19]1)[C:21]([O:23][CH3:24])=[O:22]

Participants

10

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 813631-Chloro-3-iodopropaneHCID 12034529HCID 12034529, compoundHCID 178418339Butyllithium

Product 1

HCID 66839456HCID 66839456, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-30 °C

Procedure

n-Butyl lithium (2.64 M solution in hexane, 1.1 ml) was added dropwise to a solution of diisopropylamine (0.45 ml) in THF (6 ml), and the reaction solution was stirred at −30° C. for 15 minutes. The reaction solution was cooled to −78° C. Hexamethylphosphoramide (0.75 ml) and a solution of methyl 2-(6,6-dimethyltetrahydropyran-2-yl)acetate (500 mg) in THF (3 ml) were sequentially added dropwise to the reaction solution, and the reaction solution was stirred at the same temperature for 20 minutes. 1-Chloro-3-iodopropane (0.43 ml) was added dropwise to the resulting reaction solution. The reaction solution was gradually heated, and then a saturated ammonium chloride solution was added to the reaction solution. Ethyl acetate and water were added to the reaction solution, and the organic layer was separated. The resulting 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: heptane-ethyl acetate system) to obtain 278 mg of methyl 5-chloro-2-(6,6-dimethyltetrahydropyran-2-yl)valerate.

Workup

  1. temperatureThe reaction solution was cooled to −78° C
  2. stirringthe reaction solution was stirred at the same temperature for 20 minutes
  3. temperatureThe reaction solution was gradually heated
  4. customthe organic layer was separated
  5. washThe resulting organic layer was sequentially washed with 1 N hydrochloric acid, water
  6. dry with materiala saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-4a2270a16456402395a12c2a0a9230ed
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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