Acetone → (3S, 5S)-5-[(1S)-1-(N-t-Butoxycarbonylamino)-2-cyclohexylethyl]-3-(1-hydroxy-1-methylethyl)dihydrofuran-2(3H)-one

HRID 2380118Notes

Reaction equation

HRID 2380118 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:17][C:18]([NH:20][C@H:21]([C@H:29]1[O:33][C:32](=[O:34])[CH2:31][CH2:30]1)[CH2:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[CH3:35][C:36]([CH3:38])=[O:37].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[C:13]([O:17][C:18]([NH:20][C@H:21]([C@H:29]1[O:33][C:32](=[O:34])[C@H:31]([C:36]([OH:37])([CH3:38])[CH3:35])[CH2:30]1)[CH2:22][CH:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 5

HCID 180AcetoneHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 10946873(5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-2-cyclohexylethyl]dihydrofuran-2(3H)-oneHCID 178418339Butyllithium

Product 1

HCID 14483171(3S, 5S)-5-[(1S)-1-(N-t-Butoxycarbonylamino)-2-cyclohexylethyl]-3-(1-hydroxy-1-methylethyl)dihydrofuran-2(3H)-oneYield 86%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

15.81 ml (25.3 mmoles) of a 1.6M hexane solution of butyllithium were added, at -78° C. and under an atmosphere of nitrogen, to a solution of 3.55 ml (25.3 mmoles) of diisopropylamine in 30 ml of anhydrous tetrahydrofuran. The mixture was then stirred for 30 minutes, after which a solution of 3.58 g (11.5 mmoles) of (5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-2-cyclohexylethyl]dihydrofuran-2(3H)-one (prepared as described in Preparation 5) in 10 ml of anhydrous tetrahydrofuran was added to the mixture. It was then stirred at -78° C. for 1 hour, after which 1.86 ml (25.3 mmoles) of distilled acetone was added, and the mixture was stirred for a further 2 hours. At the end of this time, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with a 10% w/v aqueous solution of citric acid, with water, and with a saturated aqueous solution of sodium chloride, in that order, and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by medium pressure silica gel column chromatography (using a 1:1 by volume mixture of hexane and diethyl ether as eluent), to give 3.65 g (yield 86%) of the title compound as the product of lesser polarity, in the form of white crystals, melting at 123°-125° C.

Workup

  1. stirringIt was then stirred at -78° C. for 1 hour
  2. stirringthe mixture was stirred for a further 2 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with a 10% w/v aqueous solution of citric acid, with water
  5. dry with materialwith a saturated aqueous solution of sodium chloride, in that order, and dried over anhydrous magnesium sulfate
  6. customThe solvent was then removed by distillation under reduced pressure
  7. customthe resulting residue was purified by medium pressure silica gel column chromatography (
  8. additionby volume mixture of hexane and diethyl ether as eluent),

Sources & evidence

ORD record
ord-8b285e72c41a4ef78fef66d201488ec1
Source dataset
uspto-grants-1994_11
Patent number
US05364844

Reaction notes

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