2-Phenylthiophene → (+/-)-(4R*,5R*)-5-[(1S*)Hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-(ethoxycarbonyl)-phenyl)-1-methylpyrrolidin-2-one

HRID 1838007Notes

Reaction equation

HRID 1838007 reaction equation
C([BH-](CC)CC)C.[Li+].ClC1[CH:11]=[C:12](C=CC=1)[O:13][CH2:14][C@@H]1N(C)C(=O)C[C@@H]1C1C=CC=CC=1.C([C@@H]1N(C)C(=O)C[C@@H]1C1C=CC=CC=1)=[O:32].C1(C2SC=CC=2)C=CC=CC=1.[Li]CCCC.[OH:62][C@H:63]([C:78]1[S:79][C:80]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)=[CH:81][CH:82]=1)[C@@H:64]1[N:68]([CH3:69])[C:67](=[O:70])[CH2:66][C@@H:65]1[C:71]1[CH:76]=[CH:75][C:74](I)=[CH:73][CH:72]=1>CCO.CC(O)=O.CC(O)=O.[Pd].CCN(CC)CC>[OH:62][C@H:63]([C:78]1[S:79][C:80]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)=[CH:81][CH:82]=1)[C@@H:64]1[N:68]([CH3:69])[C:67](=[O:70])[CH2:66][C@@H:65]1[C:71]1[CH:76]=[CH:75][C:74]([C:14]([O:13][CH2:12][CH3:11])=[O:32])=[CH:73][CH:72]=1

Participants

10

Reactant 6

HCID 699992-PhenylthiopheneHCID 13825985(-)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-oneHCID 23664628LithiumtriethylborohydrideHCID 69891684(+/-)-(4R* 5R*)-5-[(3-chlorophenoxy)methyl]-1-methyl-4-phenylpyrrolidin-2-oneHCID 69891773(+/-)-(4R*,5R*)-5-[(1S*)Hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-iodophenyl)-1-methylpyrrolidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 59066514(+/-)-(4R*,5R*)-5-[(1S*)Hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-(ethoxycarbonyl)-phenyl)-1-methylpyrrolidin-2-oneYield 67%

Reagents, catalysts & solvents 3

HCID 4144353Palladium (II) acetateCatalystHCID 702EthanolSolventHCID 8471TriethylamineSolvent

Procedure

Intermediate V was reduced with lithium triethylborohydride using the method described as Method 2 in the preparation of Intermediate T. The resulting alcohol was then subjected to Swern oxidation using the procedure described as Method I in the preparation of Intermediate Z, followed by a reaction of the resulting aldehyde with 2-phenylthiophene and n-BuLi in a manner analogous to that of Example 3a. The resulting compound, (±)-(4R*,5R*)-5-[(1S*)hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-iodophenyl)-1-methylpyrrolidin-2-one (0.100 g, 0.205 mmol), Et3N (0.1 mL) and Pd(OAC)2 (ca 10 mg) were stirred in EtOH (1 mL) under an atmosphere of carbon monoxide at 60° C. for 36 h. The resulting mixture was concentrated onto silica and the product isolated by flash chromatography (EtOAc) to yield (±)-(4R*,5R*)-5-[(1S*)hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-(ethoxycarbonyl)phenyl)-1-methyl-pyrrolidin-2-one (60 mg, 67%) as an orange solid: mp 177-179° C.; TLC (EtOAc) Rf 0.62.

Workup

  1. concentrationThe resulting mixture was concentrated onto silica
  2. customthe product isolated by flash chromatography (EtOAc)

Sources & evidence

ORD record
ord-9cd14f47f90b471f9f484fff48ed9d94
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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