Ethyl ketone → HCID 14989074, compound

HRID 2380129Notes

Reaction equation

HRID 2380129 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][CH2:36][C:37](=[O:40])[CH2:38][CH3:39].[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:37]([CH2:38][CH3:39])([OH:40])[CH2:36][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 7288Ethyl ketoneHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 10946873(5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-2-cyclohexylethyl]dihydrofuran-2(3H)-oneHCID 178418339Butyllithium

Product 1

HCID 14989074HCID 14989074, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

1.43 ml (3.58 mmoles) of butyllithium (as a 2.5M hexane solution) was added dropwise, at -78° C. and under an atmosphere of nitrogen, to a solution of 0.50 ml (3.57 mmoles) of diisopropylamine in 10 ml of anhydrous tetrahydrofuran. The mixture was then stirred for 30 minutes, after which a solution of 500 mg (1.61 mmoles) of (5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-2-cyclohexylethyl]dihydrofuran-2(3H)-one (prepared as described in Preparation 5) in 5 ml of anhydrous tetrahydrofuran was added thereto. The mixture was then stirred for a further 1 hour, and then 0.38 ml (3.59 mmoles) of distilled 3-pentanone was added to the mixture and 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, which was then 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. It was then dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by medium pressure silica gel column chromatography (using a 1:1 by volume mixture of hexane and diethyl ethyl as eluent), followed by recrystallization from hexane, to give 425 mg (yield 67%) of the title compound as white crystals, melting at 118°-120° C.

Workup

  1. stirringThe mixture was then stirred for a further 1 hour
  2. stirringstirred for a further 2 hours
  3. extractionwas then extracted with ethyl acetate
  4. washThe 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
  5. dry with materialIt was then dried over anhydrous magnesium sulfate
  6. customthe solvent was removed by distillation under reduced pressure
  7. customThe residue was purified by medium pressure silica gel column chromatography (
  8. additionby volume mixture of hexane and diethyl ethyl as eluent),
  9. customfollowed by recrystallization from hexane

Sources & evidence

ORD record
ord-de96b0fe1bfe4313aad3f4a70ea12bed
Source dataset
uspto-grants-1994_11
Patent number
US05364844

Reaction notes

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