Methyl iodide → Tert-butyl 2-[cis-3-(tert-butyldimethylsilanyloxymethyl)cyclohexylmethoxy]-2-methylpropionate

HRID 854661Notes

Reaction equation

HRID 854661 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([CH2:16]OCC(OC(C)(C)C)=O)[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:26](=[O:28])=[O:27].[CH3:29][C:30]([CH3:32])=[O:31].C([N-][CH:37]([CH3:39])[CH3:38])(C)C.[Li+].[CH3:41]I.[NH4+].[Cl-]>O1CCCC1.CCCCCC.O.O1CCCC1>[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([CH2:16][O:31][C:30]([CH3:32])([CH3:29])[C:26]([O:28][C:37]([CH3:39])([CH3:41])[CH3:38])=[O:27])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 18522661Acetone cardiceHCID 131726569Tert-butyl [cis-3-(tert-butyldimethylsilanyloxymethyl)cyclohexyl-methoxy]acetate

Product 1

HCID 131726568Tert-butyl 2-[cis-3-(tert-butyldimethylsilanyloxymethyl)cyclohexylmethoxy]-2-methylpropionate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21883165Tetrahydrofuran hexaneSolvent

Conditions

Temperature
-78 °C

Procedure

250 mg of tert-butyl [cis-3-(tert-butyidimethylsilanyloxymethyl)cyclohexyl-methoxy]acetate are dissolved in 10 ml of abs. tetrahydrofuran and cooled to −78° C. (dry ice/acetone bath). 1.70 ml of a 2M lithium diisopropylamide solution in tetrahydrofuran/hexane are then added dropwise. The solution is initially stirred at −78° C. for 20 min and then warmed to 0° C. (ice bath), and 950 mg of methyl iodide are added. The solution is stirred at 0° C. for 1 h. 1 ml of sat. NH4Cl solution and 10 ml of water are added, and the phases are separated. The aqueous phase is extracted with ethyl acetate. The combined organic phases are dried over MgSO4 and concentrated. The crude product is dissolved in 10 ml of abs. tetrahydrofuran and cooled to −78° C. (dry ice/acetone bath). 1.70 ml of a 2M lithium diisopropylamide solution in tetrahydrofuran/hexane are then added dropwise. The solution is initially stirred at −78° C. for 20 min and then warmed to 0° C. (ice bath), and 950 mg of methyl iodide are added. The solution is stirred at 0° C. for 1 h. 1 ml of sat. NH4Cl solution and 10 ml of water are added and the phases are separated. The aqueous phase is extracted with ethyl acetate. The combined organic phases are dried over MgSO4 and concentrated. This gives 220 mg of tert-butyl 2-[cis-3-(tert-butyldimethylsilanyloxymethyl)cyclo-hexylmethoxy]-2-methylpropionate as a light-yellow oil. TLC (heptane/ethyl acetate 4/1): Rf, starting material=0.66, Rf, product=0.80.

Workup

  1. additionare added
  2. stirringThe solution is stirred at 0° C. for 1 h
  3. customthe phases are separated
  4. extractionThe aqueous phase is extracted with ethyl acetate
  5. dry with materialThe combined organic phases are dried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe crude product is dissolved in 10 ml of abs
  8. temperaturetetrahydrofuran and cooled to −78° C. (dry ice/acetone bath)
  9. addition1.70 ml of a 2M lithium diisopropylamide solution in tetrahydrofuran/hexane are then added dropwise
  10. stirringThe solution is initially stirred at −78° C. for 20 min
  11. temperaturewarmed to 0° C. (ice bath), and 950 mg of methyl iodide
  12. additionare added
  13. stirringThe solution is stirred at 0° C. for 1 h
  14. addition1 ml of sat. NH4Cl solution and 10 ml of water are added
  15. customthe phases are separated
  16. extractionThe aqueous phase is extracted with ethyl acetate
  17. dry with materialThe combined organic phases are dried over MgSO4
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-4e91a26b854144289145182de93d1565
Source dataset
uspto-grants-2007_08
Patent number
US07259177B2

Reaction notes

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