Diethylaluminum chloride → (1s,3r,5s)-3-{[Tert-butyl(dimethyl)silyl]oxy}-2-methylene-5-[(triethylsilyl)oxy]cyclohexanol

HRID 388746

Reaction equation

HRID 388746 reaction equation
CC1CCCN(C)C1(C)C.C([Li])CCC.[Al](Cl)(CC)CC.[C:22]([Si:26]([CH3:45])([CH3:44])[O:27][C@@H:28]1[CH2:34][C@@H:33]([O:35][Si:36]([CH2:41][CH3:42])([CH2:39][CH3:40])[CH2:37][CH3:38])[CH2:32][C@H:31]2[C@:29]1([CH3:43])[O:30]2)([CH3:25])([CH3:24])[CH3:23]>C1C=CC=CC=1>[Si:26]([O:27][C@@H:28]1[CH2:34][C@@H:33]([O:35][Si:36]([CH2:37][CH3:38])([CH2:41][CH3:42])[CH2:39][CH3:40])[CH2:32][C@H:31]([OH:30])[C:29]1=[CH2:43])([C:22]([CH3:24])([CH3:25])[CH3:23])([CH3:44])[CH3:45]

Participants

6

Reactant 4

HCID 7277Diethylaluminum chlorideHCID 187617721,2,2,3-TetramethylpiperidineHCID 87538262Tert-butyl(dimethyl)({(1s,2r,4s,6s)-1-methyl-4-[(triethylsilyl)oxy]-7-oxabicyclo[4.1.0]hept-2-yl}oxy)silaneHCID 178418339Butyllithium

Product 1

HCID 68935721(1s,3r,5s)-3-{[Tert-butyl(dimethyl)silyl]oxy}-2-methylene-5-[(triethylsilyl)oxy]cyclohexanolYield 96.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent4×

Procedure

Tetramethylpiperidine (9.66 g, 67.7 mmol) was dissolved in 76 mL of benzene and cooled below 0° C. n-Butyllithium (2.5 M in hexane, 27.5 mL, 68.8 mmol) was added to the benzene solution below 2.5° C. The resulting solution was stirred below 0° C. Et2AlCl (1.8 M in toluene, 39 mL, 70.2 mmol) was added to the reaction below 3° C. followed by a rinse of 5.0 mL of benzene. The resulting solution was stirred at below 0° C. for 30 minutes. The compound of Example 16E (6.36 g, 17.1 mmol) dissolved in 25 mL of benzene was added to the reaction solution at below 1° C. over 10 minutes. 5.0 mL of Benzene was used as a rinse. The reaction was stirred at below 0° C. for 2.7 hours. The reaction mixture was quenched into 441 g of 17.2 wt % NH4Cl solution (cooled to below 5° C.). 104 g of 10 wt % HCl solution was slowly added to the mixture, and pH was adjusted to 2.0. The layers were separated and the aqueous layer was extracted four times with 100 mL of ethyl acetate. The combined organic layers were washed three times with 100 mL of water, then 100 mL of 7.8 wt % NaHCO3, and 100 mL of brine, and then dried over MgSO4. Filtration and concentration in vacuo yielded the title compound (6.13 g, 96%).

Workup

  1. washa rinse of 5.0 mL of benzene
  2. stirringThe resulting solution was stirred at below 0° C. for 30 minutes
  3. additionwas added to the reaction solution at below 1° C. over 10 minutes
  4. stirringThe reaction was stirred at below 0° C. for 2.7 hours
  5. customThe reaction mixture was quenched into 441 g of 17.2 wt % NH4Cl solution (cooled to below 5° C.)
  6. addition104 g of 10 wt % HCl solution was slowly added to the mixture, and pH
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted four times with 100 mL of ethyl acetate
  9. washThe combined organic layers were washed three times with 100 mL of water
  10. dry with material100 mL of 7.8 wt % NaHCO3, and 100 mL of brine, and then dried over MgSO4
  11. filtrationFiltration and concentration in vacuo

Sources & evidence

ORD record
ord-f0750ed7275a4e8aa129117051f07e28
Source dataset
uspto-grants-2013_02
Patent number
US08377913B2

Linked notes

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