Propionic Acid → 5(S)-[1(S)-(Boc-Amino)-2-cyclohexylethyl]-3(R)-[(p-methoxyphenyl)methyl]dihydrofuran-2-(3H)-one

HRID 1377151Notes

Reaction equation

HRID 1377151 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([NH:18][C@H:19]([C@H:27]1[O:31][C:30](=[O:32])[CH2:29][CH2:28]1)[CH2:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[CH3:33][O:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39]I)=[CH:37][CH:36]=1.C(O)(=O)CC.C([O-])(O)=O.[Na+]>C1COCC1.C(OCC)(=O)C.O.CN1C(=O)N(C)CCC1>[C:11]([NH:18][C@H:19]([C@H:27]1[O:31][C:30](=[O:32])[C@H:29]([CH2:39][C:38]2[CH:41]=[CH:42][C:35]([O:34][CH3:33])=[CH:36][CH:37]=2)[CH2:28]1)[CH2:20][CH:21]1[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1)([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12]

Participants

10

Reactant 5

HCID 1032Propionic AcidHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 10946873(5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-2-cyclohexylethyl]dihydrofuran-2(3H)-oneHCID 11746977p-Methoxybenzyl iodide

Product 1

HCID 157083255(S)-[1(S)-(Boc-Amino)-2-cyclohexylethyl]-3(R)-[(p-methoxyphenyl)methyl]dihydrofuran-2-(3H)-one

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-75 °C

Procedure

880 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF are added dropwise, at -70° C., under an argon atmosphere and within the space of 20 min, to 130 g (400 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-(3H)-one which is dissolved in 1000 ml of abs. THF and 108 ml of DMPU. After 20 min, a solution of 110 g (443 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 60 ml of abs. THF is added dropwise, and this mixture is thoroughly stirred at -75° C. for 2 h. The mixture is subsequently protonate at -70° C. with 152 ml of propionic acid followed by 250 ml of water (temperature rises to -20° C.); 1 l of ethyl acetate is then added and the reaction mixture is poured onto 2 l of 15% NaHCO3 solution. The aqueous phase is separated off and extracted with 1 l of ethyl acetate. The organic phases are washed 2× with sat. NaHCO3 solution, water and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane yields the pure title compound: TLC Rf (E)=0.45; tRet (II)=18.6 min; FAB-MS (M+H)+ =432.

Workup

  1. dissolutionis dissolved in 1000 ml of abs
  2. customThe aqueous phase is separated off
  3. extractionextracted with 1 l of ethyl acetate
  4. washThe organic phases are washed 2× with sat. NaHCO3 solution, water and saline
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customColumn chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane

Sources & evidence

ORD record
ord-328d322add9743b4b3cabe8948532d97
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

Loading…