Sodium borohydride → (4R)-4-(1-Hydroxypropyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2208985Notes

Reaction equation

HRID 2208985 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([N:11]2[CH2:15][C@H:14]([C:16](=[O:19])[CH2:17][CH3:18])[CH2:13][C:12]2=[O:20])[CH3:10])=[CH:5][CH:4]=1.[BH4-].[Na+]>C(O)C>[OH:19][CH:16]([C@H:14]1[CH2:15][N:11]([C@@H:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH3:10])[C:12](=[O:20])[CH2:13]1)[CH2:17][CH3:18]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 117843004(R)-1-((R)-1-(4-Methoxyphenyl)ethyl)-4-propionylpyrrolidin-2-one

Product 1

HCID 117843409(4R)-4-(1-Hydroxypropyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed (4R)-1-[(1R)-1-(4-methoxyphenyl)ethyl]-4-propanoylpyrrolidin-2-one 1.22 (6 g, 21.79 mmol, 1.00 equiv), ethanol (60 mL), followed by the addition of NaBH4 (1.85 g, 48.68 mmol, 2.50 equiv) in several batches with stifling at 0° C. The resulting solution was stirred at room temperature for 2 h, quenched by the addition of 100 mL of water/ice, extracted with 3×200 mL of ethyl acetate. The organic layers were combined, washed with 2×200 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was washed with 1×100 mL of ether and the solids were collected by filtration to afford (4R)-4-(1-hydroxypropyl)-1-[(1R)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-one as a mixture of diastereomers. The diastereomers were separated by chiral HPLC (CHIRALPAK AD), and the earlier eluting diastereomer was collected to afford (R)-4-((R)-1-hydroxypropyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.23. This compound is the later eluting diastereomer under RP-HPLC conditions (Gemini column, water/acetonitrile/TFA).

Workup

  1. customInto a 250-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customwith stifling at 0° C
  4. customquenched by the addition of 100 mL of water/ice
  5. extractionextracted with 3×200 mL of ethyl acetate
  6. washwashed with 2×200 mL of brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. washThe residue was washed with 1×100 mL of ether
  10. filtrationthe solids were collected by filtration

Sources & evidence

ORD record
ord-c0d2ac7d194f4b209be8e0bb223ff445
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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