Methyl iodide → Methyl 4-[(tert-butyldimethylsilyl)oxy]-1-methylcyclohexane-1-carboxylate

HRID 1504035Notes

Reaction equation

HRID 1504035 reaction equation
[Li][CH2:2]CCC.[Si:6]([O:13][CH:14]1[CH2:19][CH2:18][CH:17]([C:20]([O:22][CH3:23])=[O:21])[CH2:16][CH2:15]1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].CI>C1COCC1>[Si:6]([O:13][CH:14]1[CH2:15][CH2:16][C:17]([CH3:2])([C:20]([O:22][CH3:23])=[O:21])[CH2:18][CH2:19]1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:7])[CH3:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 22167752Methyl trans-4-[(tert-butyldimethylsilyl)oxy]cyclohexanecarboxylateHCID 178418339Butyllithium

Product 1

HCID 86695195Methyl 4-[(tert-butyldimethylsilyl)oxy]-1-methylcyclohexane-1-carboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of anhydrous DIPA (26.7 g, 263.86 mmol, 3.00 equiv) in freshly distilled THF (500 mL) was added n-BuLi (2.5 M in hexane, 110 mL) dropwise with stirring at −78° C. under nitrogen. After the addition, the resulting solution was stirred for 0.5 h at −78° C. To this was added dropwise a solution of methyl 4-[(tert-butyldimethylsilyl)oxy]cyclohexane-1-carboxylate (24 g, 88.09 mmol, 1.00 equiv) in 50 mL of THF and the resulting solution was allowed to react for an additional 1 h at −78° C. To the mixture was added CH3I (62.64 g, 441.31 mmol, 5.01 equiv) dropwise with stirring at this low temperature. Stirring was continued for 1 h. The reaction was quenched with water and extracted with 3×150 mL of ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/10) to provide the desired methyl 4-[(tert-butyldimethylsilyl)oxy]-1-methylcyclohexane-1-carboxylate (22.0 g, 87%) as a colorless oil.

Workup

  1. additionAfter the addition
  2. stirringthe resulting solution was stirred for 0.5 h at −78° C
  3. customto react for an additional 1 h at −78° C
  4. stirringwith stirring at this low temperature
  5. stirringStirring
  6. customThe reaction was quenched with water
  7. extractionextracted with 3×150 mL of ethyl acetate
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5a920e3560e4496db406ad9363642857
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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