Diethyl Malonate → (5R)-5-[(1S)-1-[[(1,1-Dimethylethoxy)carbonyl]amino]-2-phenylethyl]tetrahydro-2-oxo-3-furancarboxylic Acid Ethyl Ester

HRID 1174281Notes

Reaction equation

HRID 1174281 reaction equation
[O:1]1[CH2:3][C@@H:2]1[C@@H:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:20](OCC)(=O)[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23].CC[O-:33].[Na+]>C(O)C>[C:15]([O:14][C:13]([NH:12][C@H:4]([C@@H:2]1[O:1][C:3](=[O:33])[CH:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:20]1)[CH2:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:19])([CH3:16])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 2723922Sodium ethoxideHCID 9903372(2S,3S)-(-)-3-tert-Butoxycarbonylamino-1,2-epoxy-4-phenylbutane

Product 1

HCID 13884421(5R)-5-[(1S)-1-[[(1,1-Dimethylethoxy)carbonyl]amino]-2-phenylethyl]tetrahydro-2-oxo-3-furancarboxylic Acid Ethyl EsterYield 93%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A solution of tert-Butyl(1S)-1-[(2S)-oxiran-2-yl]-2-phenylethylcarbamate (10.0 g, 38.0 mmol) and diethyl malonate (9.0 ml, 59.3 mmol) in ethanol (27 mL) at 0° C. was treated with a solution of NaOEt (16 mL, 21% in ethanol) over 10 minutes, stirred at 70° C. for 2 hours, cooled to 0° C. and quenched with 10% citric acid solution, and partitioned between ethyl acetate and water. The organic phase was washed with saturated NaHCO3and brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-35% ethyl acetate in hexanes to give the title compound (13.3 g, 93% yield).

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with 10% citric acid solution
  3. custompartitioned between ethyl acetate and water
  4. washThe organic phase was washed with saturated NaHCO3and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel eluting with 0-35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-54d7aa6143704e828fbfdc5f80b240b4
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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