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

HRID 1768846Notes

Reaction equation

HRID 1768846 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+]>CCCCCC.O1CCCC1>[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 mmole) of butyllithium (as a 1.6M solution in hexane) were added, at -78° C. and under an atmosphere of nitrogen, to a solution of 3.55 ml (25.3 mmole) of diisopropylamine in 30 ml of anhydrous tetrahydrofuran, and the mixture was stirred for 30 minutes. A solution of 3.58 g (11.5 mmole) of (5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]dihydrofuran-2(3H)-one in 10 ml of anhydrous tetrahydrofuran was then added to the mixture, and the mixture was stirred at -78° C. for 1 hour. 1.86 ml (25.3 mmole) of acetone purified by distillation was added to the mixture, after which the mixture was stirred for a further 2 hours. At the end of this time, the reaction mixture was mixed with a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed, in turn, with a 10% w/v aqueous solution of citric acid, with water and with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure and the residue was purified by medium pressure column chromatography through silica gel (using a 1:1 by volume mixture of hexane and diethyl ether as the eluent). The title compound, obtained from the less polar fractions, was isolated as white crystals, melting at 123°-125° C., and the amount obtained was 3.65 g (yield 86%).

Workup

  1. stirringthe mixture was stirred at -78° C. for 1 hour
  2. additionwas added to the mixture
  3. stirringafter which the mixture was stirred for a further 2 hours
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed, in turn, with a 10% w/v aqueous solution of citric acid, with water and with a saturated aqueous solution of sodium chloride
  6. dry with materialafter which it was dried over anhydrous magnesium sulfate
  7. customThe solvent was then removed by distillation under reduced pressure
  8. customthe residue was purified by medium pressure column chromatography through silica gel (
  9. additionby volume mixture of hexane and diethyl ether as the eluent)

Sources & evidence

ORD record
ord-476b4d1621554e53b6d25ece4f8a4f13
Source dataset
uspto-grants-1995_01
Patent number
US05378689

Reaction notes

Loading…