Diisopropylamine → HCID 178455043, compound

HRID 516893Notes

Reaction equation

HRID 516893 reaction equation
C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[Si:19]([O:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:36])=[CH:29][CH:28]=1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].[Si:45]([O:52][C@@H:53]1[CH2:58][CH2:57][C@H:56]([C:59](=[O:70])[C:60]([O:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)=[O:61])[CH2:55][CH2:54]1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]>C1COCC1>[Si:19]([O:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH:34]([C:35]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:36])[C:59]([C@H:56]2[CH2:57][CH2:58][C@@H:53]([O:52][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:46])[CH3:47])[CH2:54][CH2:55]2)([OH:70])[C:60]([O:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)=[O:61])=[CH:29][CH:28]=1)([C:22]([CH3:24])([CH3:25])[CH3:23])([CH3:21])[CH3:20]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 8058HexaneHCID 59706501Benzyl 3-(4-((tert-butyldimethylsilyl)oxy)phenyl)propanoateHCID 178418339ButyllithiumHCID 178455323HCID 178455323, compound

Product 1

HCID 178455043HCID 178455043, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A 2.5 M n-butyllithium solution in hexane (0.49 ml, 1.22 mmol) was added to a solution of diisopropylamine (0.18 ml, 1.29 mmol) in anhydrous THF (3.0 ml) at −78° C. under an argon stream. The mixture was brought to 0° C., and the mixture was stirred for 30 min and was again cooled to −78° C. A solution of benzyl 3-(4-((tert-butyldimethylsilyl)oxy)phenyl)propanoate (300 mg, 0.81 mmol) in anhydrous THF (4.0 ml) was added dropwise thereto at −78° C., and the mixture was stirred for additional one hr. A solution of benzyl 2-(cis-4-((tert-butyldimethylsilyl)oxy)cyclohexyl)-2-oxoacetate (304 mg, 0.81 mmol) in anhydrous THF (4.0 ml) that had been cooled to −78° C. was added through a cannula to the resultant enolate solution over 10 min. The mixture was stirred at −78° C. for one hr, was quenched and adjusted to pH 4 with acetic acid and was allowed to cool to room temperature. The reaction solvent was removed by distillation under reduced pressure, and the residue was diluted with ethyl acetate, and the diluted solution was washed with water and saturated brine and was dried over anhydrous magnesium sulfate. The filtrate was concentrated under reduced pressure. The residue was chromatographed on silica gel column (hexane:ethyl acetate=95:5) to give the title compound as an oil (a diastereomeric mixture; 120 mg, yield 19%).

Workup

  1. customwas brought to 0° C.
  2. stirringat −78° C., and the mixture was stirred for additional one hr
  3. stirringThe mixture was stirred at −78° C. for one hr
  4. customwas quenched
  5. temperatureto cool to room temperature
  6. customThe reaction solvent was removed by distillation under reduced pressure
  7. additionthe residue was diluted with ethyl acetate
  8. washthe diluted solution was washed with water and saturated brine
  9. dry with materialwas dried over anhydrous magnesium sulfate
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customThe residue was chromatographed on silica gel column (hexane:ethyl acetate=95:5)

Sources & evidence

ORD record
ord-2e133f791a0e4c2eb26733fc0eb9cd17
Source dataset
uspto-grants-2015_08
Patent number
US09115079B2

Reaction notes

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