Chlorotrimethylsilane → HCID 86758572, compound

HRID 991866Notes

Reaction equation

HRID 991866 reaction equation
C[Li].CN(C)P(N(C)C)(N(C)C)=O.[CH3:14][C:15]1[CH2:20][CH2:19][CH2:18][C:17](=[O:21])[C:16]=1[CH:22]=[CH:23][C:24]#[C:25][C:26]1[CH:40]=[CH:39][C:29]([C:30]([O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])=[O:31])=[CH:28][CH:27]=1.Cl[Si](C)(C)[CH3:43]>CSC.[Cu]Br.CCOCC.N1C=CC=CC=1.C1COCC1>[CH3:14][C:15]1([CH3:43])[CH2:20][CH2:19][CH2:18][C:17](=[O:21])[CH:16]1/[CH:22]=[CH:23]/[C:24]#[C:25][C:26]1[CH:27]=[CH:28][C:29]([C:30]([O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:38])[CH3:37])=[O:31])=[CH:39][CH:40]=1

Participants

9

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 12679HexamethylphosphoramideHCID 57027195HCID 57027195, compound2×HCID 178418348HCID 178418348, compound

Product 1

HCID 86758572HCID 86758572, compound

Reagents, catalysts & solvents 4

HCID 2724234Bromo(thiobis(methane))copperCatalystHCID 1049PyridineSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A 1.3 M solution of methyllithium (3.8 mL, 5.26 mmol) was added to a stirring suspension of copper (I) bromide-dimethyl sulfide (541 mg, 2.63 mmol) and 10 mL of THF at −78° C. The solution was warmed to −40° C. over 30 minutes and then re-cooled to −78° C. Freshly distilled hexamethylphosphoramide (0.685 mL, 3.94 mmol) was added, and the solution was stirred at −78° C. for 30 minutes. A solution of (trimethylsilyl)ethyl 4-(4-(2-methyl-6-oxocyclohex-1-enyl)but-3-en-1-ynyl)benzoate (Compound D, 500 mg, 1.31 mmol), chlorotrimethylsilane (0.50 mL, 3.94 mmol) and 2.5 mL of THF was added. After the solution was stirred at −78° C. for 1 hour, pyridine (0.159 mL) and ether (0.5 mL) were added. The reaction was then quenched by the addition of 5% aqueous NaHCO3. The layers were separated and the aqueous layer extracted 3 times with ethyl acetate. The combined organic layers were washed with 10% aqueous HCl until all of the enol ether was hydrolyzed. The layers were separated and the organic layer was washed with water, and brine, and dried (MgSO4). The solvents were removed under reduced pressure, and the residue was purified by silica gel chromatography (10:1, hexane:ethyl acetate) to give the title compound as a yellow solid.

Workup

  1. temperaturere-cooled to −78° C
  2. stirringAfter the solution was stirred at −78° C. for 1 hour
  3. customThe reaction was then quenched by the addition of 5% aqueous NaHCO3
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted 3 times with ethyl acetate
  6. washThe combined organic layers were washed with 10% aqueous HCl until all of the enol ether
  7. customThe layers were separated
  8. washthe organic layer was washed with water, and brine
  9. dry with materialdried (MgSO4)
  10. customThe solvents were removed under reduced pressure
  11. customthe residue was purified by silica gel chromatography (10:1, hexane:ethyl acetate)

Sources & evidence

ORD record
ord-98b4bcef574745428f5e36ee88f277ca
Source dataset
uspto-grants-2002_10
Patent number
US06465646B1

Reaction notes

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