Lithium Chloride → Ethyl 4-[(7,8-dihydro-8,8-dimethyl-5-(1,1-dimethylethyl)naphth-3-yl)ethynyl]benzoate

HRID 265780Notes

Reaction equation

HRID 265780 reaction equation
[Cl-].[Li+].[C:3]([Li])([CH3:6])([CH3:5])[CH3:4].FC(F)(F)S(O[C:14]1[C:15]2[CH:16]=[C:17]([C:26]#[C:27][C:28]3[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=3)[CH:18]=[CH:19][C:20]=2[C:21]([CH3:25])([CH3:24])[CH2:22][CH:23]=1)(=O)=O>C1COCC1>[CH3:4][C:3]1([CH3:6])[C:14]2[CH:23]=[CH:18][C:17]([C:26]#[C:27][C:28]3[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=3)=[CH:16][C:15]=2[C:20]([C:21]([CH3:22])([CH3:24])[CH3:25])=[CH:19][CH2:5]1

Participants

5

Reactant 3

HCID 433294Lithium ChlorideHCID 120176384-[2-[5,6-Dihydro-5,5-dimethyl-8-[[(trifluoromethyl)sulfonyl]oxy]-2-naphthalenyl]ethynyl]benzoic acid ethyl ester2×HCID 178418306HCID 178418306, compound

Product 1

HCID 18314564Ethyl 4-[(7,8-dihydro-8,8-dimethyl-5-(1,1-dimethylethyl)naphth-3-yl)ethynyl]benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 35.1 mg (0.39 mmol) of cuprous cyanide and 16.6 mg (0.39 mmol) of lithium chloride was flame dried under vacuum, cooled to room temperature and dissolved in 1.5 ml of THF. This solution was cooled to -78° C. and 50.2 mg (0.46 mL, 0.784 mmol) of tert-butyllithium (1.7M solution in pentane) was added forming a clear yellow solution. The reaction mixture was stirred at -78° C. for 15 minutes and then 125.0 mg (0.26 mmol) of ethyl 4-[(5-trifluoromethylsulfonyloxy-7,8-dihydro-8,8-dimethylnaphth-3-yl)ethynyl]benzoate (Compound 66) was added as a solution in 0.5 ml of THF. After 10 minutes the reaction was quenched at -78° C. with 1.5 ml of a 2:1 (v/v) mixture of sat. aqueous NH4Cl and 5% NaOH. The mixture was extracted with EtOAc and the combined organic layers were washed with water and brine. The organic phase was dried over MgSO4, concentrated in vacuo and purified by column chromatography (silica, 5% EtOAc-hexanes) to give a clear yellow oil (7:5 ratio of title compounds). The two compounds were separated by HPLC (partisil 10, 2% EtOAc-hexanes) to give the title compounds as colorless oils.

Workup

  1. temperaturewas flame
  2. customdried under vacuum
  3. dissolutiondissolved in 1.5 ml of THF
  4. temperatureThis solution was cooled to -78° C.
  5. customforming a clear yellow solution
  6. customAfter 10 minutes the reaction was quenched at -78° C. with 1.5 ml of a 2:1 (v/v) mixture of sat. aqueous NH4Cl and 5% NaOH
  7. extractionThe mixture was extracted with EtOAc
  8. washthe combined organic layers were washed with water and brine
  9. dry with materialThe organic phase was dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. custompurified by column chromatography (silica, 5% EtOAc-hexanes)
  12. customto give a clear yellow oil (7:5 ratio of title compounds)
  13. customThe two compounds were separated by HPLC (partisil 10, 2% EtOAc-hexanes)

Sources & evidence

ORD record
ord-134693a0a9e344248faa695f74215374
Source dataset
uspto-grants-1997_07
Patent number
US05648514

Reaction notes

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