HCID 22851707, compound → 2(S)-acetamido-3(S)-methoxycarbonyl-4(R)-pentanolide

HRID 55458Notes

Reaction equation

HRID 55458 reaction equation
[C:1]([NH:4][C:5]1[C:6]([O:8][C@H:9]([CH3:15])[C:10]=1[C:11]([O:13][CH3:14])=[O:12])=[O:7])(=[O:3])[CH3:2]>CO.[Pd]>[C:1]([NH:4][C@H:5]1[C@H:10]([C:11]([O:13][CH3:14])=[O:12])[C@@H:9]([CH3:15])[O:8][C:6]1=[O:7])(=[O:3])[CH3:2]

Participants

4

Reactant 1

HCID 22851707HCID 22851707, compound

Product 1

HCID 110093242(S)-acetamido-3(S)-methoxycarbonyl-4(R)-pentanolide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

169.2 g of (R)-2-acetamido-3-methoxycarbonyl-2-penten-4-olide are dissolved in 800 ml of methanol, 10 g of Pd/C (5%) are added and the whole is hydrogenated for 8 hours at 30° C. and 3-5 bars. The catalyst is filtered off, washed with methanol and the filtrate is concentrated by evaporation. The ratio of the diastereoisomers of the crude product exhibited by HPLC analysis is (2S,3S,4R):(2R,3S,4R):(2S,3R,4R)=approximately 5:3:2. The proportion of the (2R,3R,4R)-diastereoisomer is less than 1%. The mixture is dissolved in 500 ml of methanol, 12 g of 1,8-diazabicyclo[5.4.0]undec-7-ene are added and the whole is stirred at room temperature for 48 hours, resulting in a mixture, 86-88% of which consists of the desired (2S,3S,4R)-diastereoisomer. The solution is concentrated, neutralised with 2N hydrochloric acid, taken up in ethyl acetate and extracted with saturated sodium chloride solution. Diastereoisomerically pure title compound is obtained by crystallisation from ethyl acetate/cyclohexane, [α]D20 =-49.5° (3% in CH3OH), m.p. 105°-106° C., IR 1787, 1740, 1689, 1510 cm-1.

Workup

  1. filtrationThe catalyst is filtered off
  2. washwashed with methanol
  3. concentrationthe filtrate is concentrated by evaporation
  4. dissolutionThe mixture is dissolved in 500 ml of methanol
  5. addition12 g of 1,8-diazabicyclo[5.4.0]undec-7-ene are added
  6. customresulting in a mixture, 86-88% of which
  7. concentrationThe solution is concentrated
  8. extractionextracted with saturated sodium chloride solution

Sources & evidence

ORD record
ord-289973f03fb346f08f0903e8f6f1d6b8
Source dataset
uspto-grants-1997_04
Patent number
US05625059

Reaction notes

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