Lithium diisopropylamide → HCID 22490963, compound

HRID 2180599Notes

Reaction equation

HRID 2180599 reaction equation
[Br:1][C:2]1[C:11]2[C:10]([CH3:13])([CH3:12])[CH2:9][CH:8]=[C:7]([CH:14]([CH3:16])[CH3:15])[C:6]=2[CH:5]=[C:4]([C:17](=[O:19])[CH3:18])[C:3]=1[O:20][CH2:21][CH3:22].[CH:23]([N-]C(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[C:11]2[C:10]([CH3:13])([CH3:12])[CH2:9][CH:8]=[C:7]([CH:14]([CH3:16])[CH3:15])[C:6]=2[CH:5]=[C:4]([C:17](=[O:19])[CH2:18][CH3:23])[C:3]=1[O:20][CH2:21][CH3:22]

Participants

4

Reactant 2

HCID 2724682Lithium diisopropylamideHCID 22490930HCID 22490930, compound

Product 1

HCID 22490963HCID 22490963, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-(4-bromo-3-ethoxy-8-isopropyl-5,5-dimethyl-5,6-dihydro-naphthalen-2-yl)-ethanone (Compound A-109, 1.75 g, 4.81 mmol) in THF (33 mL) at −78° C. was added lithium diisopropylamide (1.5 M in cyclohexane, 3.85 mL, 5.78 mmol). The bath was removed and the mixture was stirred for 2.5 h. The mixture was cooled to −78° C. again and methyl iodide was added. The mixture was stirred at room temperature for 16 h, quenched with saturated ammonium chloride, and extracted with diethyl ether. The combined ethereal layers were washed with water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by flash chromatography (silica gel, 2% ethyl acetate in hexanes) followed by HPLC (normal phase, 2% ethyl acetate in hexanes) to give the title compound as clear oil.

Workup

  1. customThe bath was removed
  2. additionmethyl iodide was added
  3. stirringThe mixture was stirred at room temperature for 16 h
  4. customquenched with saturated ammonium chloride
  5. extractionextracted with diethyl ether
  6. washThe combined ethereal layers were washed with water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by flash chromatography (silica gel, 2% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-87e9310f14634225a98a2a9c6779e55c
Source dataset
uspto-grants-2005_05
Patent number
US06887896B1

Reaction notes

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