Ethanol → (2R,4R)-4-amino-5-biphenyl-4-yl-2-hydroxypentanoic acid ethyl ester

HRID 2273472Notes

Reaction equation

HRID 2273472 reaction equation
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[N:12](C(=O)C(C)(C)C)[C:11](=[O:19])[C@H:10]([OH:20])[CH2:9]2)=[CH:3][CH:2]=1.[CH3:27][CH2:28][OH:29]>Cl.Cl.CCO>[CH2:28]([O:29][C:11](=[O:19])[C@H:10]([OH:20])[CH2:9][C@H:8]([NH2:12])[CH2:7][C:4]1[CH:3]=[CH:2][C:1]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[CH:6][CH:5]=1)[CH3:27]

Participants

5

Reactant 2

HCID 702EthanolHCID 67969475(3R,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-hydroxypyrrolidin-2-one

Product 1

HCID 67969400(2R,4R)-4-amino-5-biphenyl-4-yl-2-hydroxypentanoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 21887872Ethanol hydrochlorideSolvent

Procedure

(3R,5R)-5-Biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-hydroxypyrrolidin-2-one (56 g, 0.156 mol) was dissolved in EtOH (700 mL) and 12N HCl (700 mL). The mixture was heated to 90˜95° C. for 20 hours. The mixture was concentrated on an 80° C. water bath under reduced pressure. EtOH (100 mL) was added to the residue, and the resulting mixture was filtered to yield a yellow solid. This solid was suspended in 3N HCl/EtOH (800 mL). The mixture was refluxed for 3 hours. The solution was concentrated to a reduced volume (˜200 mL volume), and ether (200 mL) was added. The resulting slightly yellow solid was filtered and dried under reduced pressure to yield (2R,4R)-4-amino-5-biphenyl-4-yl-2-hydroxypentanoic acid ethyl ester (43 g).

Workup

  1. temperatureThe mixture was heated to 90˜95° C. for 20 hours
  2. concentrationThe mixture was concentrated on an 80° C. water bath under reduced pressure
  3. additionEtOH (100 mL) was added to the residue
  4. filtrationthe resulting mixture was filtered
  5. customto yield a yellow solid
  6. temperatureThe mixture was refluxed for 3 hours
  7. concentrationThe solution was concentrated to a reduced volume (˜200 mL volume), and ether (200 mL)
  8. additionwas added
  9. filtrationThe resulting slightly yellow solid was filtered
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-03fe0b0eedb141e1a703b5ebae91ef68
Source dataset
uspto-grants-2015_09
Patent number
US09120747B2

Reaction notes

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