Cyclohexanone → (2R,5S)-2-tert-Butyl-5-(1-hydroxy-cyclohexyl)-5-phenyl-[1,3]dioxolan-4-one

HRID 660081Notes

Reaction equation

HRID 660081 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([C@H:15]1[O:19][C:18](=[O:20])[CH:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:16]1)([CH3:14])([CH3:13])[CH3:12].[C:27]1(=[O:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>C1COCC1>[C:11]([C@H:15]1[O:19][C:18](=[O:20])[C@@:17]([C:27]2([OH:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:16]1)([CH3:14])([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 2733832Lithium HexamethyldisilazideHCID 67538722(R)-2-tert-butyl-5-phenyl-[1,3]dioxolan-4-one

Product 1

HCID 67538099(2R,5S)-2-tert-Butyl-5-(1-hydroxy-cyclohexyl)-5-phenyl-[1,3]dioxolan-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) solution of 1 M lithium bis(trimethylsilyl)amide in hexanes (1 litre, 1 mol) is added dropwise (R)-2-tert-butyl-5-phenyl-[1,3]dioxolan-4-one (170 g, 0.77 mol) in THF (1.1 litre) over 90 minutes ensuring the temperature does not exceed −70° C. After stirring at −78° C. for 1 hour, cyclohexanone (112 ml, 1.1 mol) is added dropwise over 15 minutes and then stirring continued at −78° C. for another hour. The reaction is quenched by addition of 10% aqueous ammonium chloride solution (170 ml) and after warming to −20° C., a further 2 litres of 10% aqueous ammonium chloride solution is added. The aqueous portion is separated and extracted with EtOAc (500 ml). The organic portions are combined, dried over MgSO4 and concentrated in vacuo. The resulting crude product is slurried in heptane for 20 minutes and then filtered and dried in vacuo to afford the titled compound as a white solid.

Workup

  1. customdoes not exceed −70° C
  2. stirringstirring
  3. waitcontinued at −78° C. for another hour
  4. customThe reaction is quenched by addition of 10% aqueous ammonium chloride solution (170 ml)
  5. temperatureafter warming to −20° C.
  6. additiona further 2 litres of 10% aqueous ammonium chloride solution is added
  7. customThe aqueous portion is separated
  8. extractionextracted with EtOAc (500 ml)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. waitThe resulting crude product is slurried in heptane for 20 minutes
  12. filtrationfiltered
  13. customdried in vacuo

Sources & evidence

ORD record
ord-c763dcc8b5b94367913de4ff256a7fd0
Source dataset
uspto-grants-2011_12
Patent number
US08084463B2

Reaction notes

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