Diisopropylamine → 8-t-Butyldimethylsilyloxy-1-(2,2-Dimethyl-1,3-Dioxolan-4-yl)-2-Hydroxyoctan-4-One

HRID 1194141Notes

Reaction equation

HRID 1194141 reaction equation
C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[Si:19]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31](=[O:33])[CH3:32])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].[CH3:34][C:35]1([CH3:43])[O:39][CH:38]([CH2:40][CH:41]=[O:42])[CH2:37][O:36]1>C1COCC1.O>[Si:19]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31](=[O:33])[CH2:32][CH:41]([OH:42])[CH2:40][CH:38]1[CH2:37][O:36][C:35]([CH3:43])([CH3:34])[O:39]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8058HexaneHCID 109223462-Hexanone, 6-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-HCID 109863582-(2,2-Dimethyl-1,3-dioxolan-4-yl)acetaldehydeHCID 178418339Butyllithium

Product 1

HCID 103173088-t-Butyldimethylsilyloxy-1-(2,2-Dimethyl-1,3-Dioxolan-4-yl)-2-Hydroxyoctan-4-One

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of n-butyl lithium in hexane (119 ml, 1.6M, 0.19 mol) is added dropwise to a solution of diisopropylamine (19.3 g, 0.191 mol) in THF (100 ml) cooled in an ice bath. After the addition, the mixture is stirred for 20 minutes then cooled to -78°. A solution of 6-t-butyldimethylsilyloxy-hexan-2-one (40.0 g, 0.174 mol) in THF is added dropwise. The resultant mixture is stirred for 90 minutes then a solution of 2,2-dimethyl-1,3-dioxolane-4-acetaldehyde (25.1 g, 0.174 mol) in THF (100 ml) is added dropwise. After the addition, the mixture is stirred for 2 hours, then water (10 ml) slowly added. The mixture is warmed to 0°, diluted with water (300 ml) and extracted with ether (2×500 ml). The extracts are washed with saturated brine, dried over sodium sulfate and concentrated under reduced pressure to leave the crude product (63.5 g) an oil. A portion of this material (46 g) is chromatographed on silica gel (2.5 Kg) eluting with 25% ethyl acetate/hexane to give the title compound, 8-t-butyldimethylsiloxy-1-(2,2-dimethyl-1,3-doxolan-4-yl)-2-hydroxyoctan-4-one; (23 g, 49%) an oil.

Workup

  1. temperaturecooled in an ice bath
  2. additionAfter the addition
  3. temperaturethen cooled to -78°
  4. additionAfter the addition
  5. stirringthe mixture is stirred for 2 hours
  6. temperatureThe mixture is warmed to 0°
  7. extractionextracted with ether (2×500 ml)
  8. washThe extracts are washed with saturated brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto leave the crude product (63.5 g) an oil
  12. customA portion of this material (46 g) is chromatographed on silica gel (2.5 Kg)
  13. washeluting with 25% ethyl acetate/hexane

Sources & evidence

ORD record
ord-d85f089b07cd4b2cacd775ee60f2b02d
Source dataset
uspto-grants-1989_03
Patent number
US04812582

Reaction notes

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