Chlorotrimethylsilane → HCID 86752691, compound

HRID 991868Notes

Reaction equation

HRID 991868 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:36]=[CH:35][C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][CH:27]=1.Cl[Si](C)(C)[CH3:39]>CSC.[Cu]Br.C1COCC1>[CH3:14][C:15]1([CH3:39])[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][CH3:34])=[O:31])=[CH:35][CH:36]=1

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 12679HexamethylphosphoramideHCID 56987556HCID 56987556, compound2×HCID 178418348HCID 178418348, compound

Product 1

HCID 86752691HCID 86752691, compound

Reagents, catalysts & solvents 2

HCID 2724234Bromo(thiobis(methane))copperCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

1.3 M solution of methyllithium (2.2 mL, 2.85 mmol) was added to a stirring suspension of copper (I) bromide-dimethyl sulfide (293 mg, 1.43 mmol) and 6 mL of THF at −78° C. The solution was warmed to −40° C. over 30 minutes and then recooled to −78° C. Freshly distilled hexamethylphosphoramide (0.37 mL, 2.14 mmol) was added, and the solution was stirred at −78° C. for 30 minutes. A solution of ethyl 4-(4-(2-methyl-6-oxocyclohex-1-enyl)but-3-en-1-ynyl)benzoate (Compound H, 220 mg, 0.713 mmol), chlorotrimethylsilane (0.271 mL, 2.14 mmol) and 1.5 mL of THF was added. The solution was stirred at −78° C. for 1 hour, and warmed slowly to −30° C. The reaction was then quenched by the addition of saturated aqueous NH4Cl and ethyl acetate. 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 oil.

Workup

  1. customrecooled to −78° C
  2. stirringThe solution was stirred at −78° C. for 1 hour
  3. temperaturewarmed slowly to −30° C
  4. customThe reaction was then quenched by the addition of saturated aqueous NH4Cl and ethyl acetate
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted 3 times with ethyl acetate
  7. washThe combined organic layers were washed with 10% aqueous HCl until all of the enol ether
  8. customThe layers were separated
  9. washthe organic layer was washed with water, and brine
  10. dry with materialdried (MgSO4)
  11. customThe solvents were removed under reduced pressure
  12. customthe residue was purified by silica gel chromatography (10:1, hexane:ethyl acetate)

Sources & evidence

ORD record
ord-8289ea0b6fa547e4b5d662eeb1979e2b
Source dataset
uspto-grants-2002_10
Patent number
US06465646B1

Reaction notes

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