Stannous chloride dihydrate → (+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-one

HRID 1838003Notes

Reaction equation

HRID 1838003 reaction equation
C([BH-]([CH2:6][CH3:7])CC)C.[Li+].ClC1C=C(C=CC=1)[O:13][CH2:14][C@@H:15]1[N:19]([CH3:20])[C:18](=[O:21])[CH2:17][C@@H:16]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([C@@H]1N(C)C(=O)C[C@@H]1[C:40]1[CH:45]=[CH:44][CH:43]=CC=1)=O.C1([C:52]2[S:53][CH:54]=[CH:55][CH:56]=2)C=CC=CC=1.[Li]CCCC.O[C@H](C1SC(C2C=CC=CC=2)=CC=1)[C@@H]1[N:68](C)C(=O)C[C@@H]1C1C=CC([N+]([O-])=O)=CC=1.O.O.[Sn](Cl)Cl.C([O-])(O)=O.[Na+]>CCO>[OH:13][C@H:14]([C:52]1[S:53][C:54]([C:7]2[CH:6]=[CH:43][CH:44]=[CH:45][CH:40]=2)=[CH:55][CH:56]=1)[C@@H:15]1[N:19]([CH3:20])[C:18](=[O:21])[CH2:17][C@@H:16]1[C:22]1[CH:23]=[CH:24][C:25]([NH2:68])=[CH:26][CH:27]=1

Participants

10

Reactant 8

HCID 61436Stannous chloride dihydrateHCID 699992-PhenylthiopheneHCID 516892Sodium BicarbonateHCID 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 69892691(+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-nitrophenyl)-1-methylpyrrolidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 10271018(+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-oneYield 60%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

The ester of Intermediate U step 1 was reduced with lithium triethylborohydride using the procedure 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 1 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. To the resulting product, (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-nitrophenyl)-1-methylpyrrolidin-2-one (110 mg, 0.27 mmol), in EtOH (10 mL) was added tin(II) chloride dihydrate (312 mg, 1.38 mmol, 5 equiv), and the resulting mixture was heated at 70° C. for 2.5 h, then allowed to cool to room temperature and poured onto ice water. A saturated NaHCO3 solution was added to adjust the mixture to pH 8. The basic mixture was extracted with EtOAc, dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (EtOAc) to give (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-one (63 mg, 60%) as a yellow solid: mp 221-222° C.; TLC (EtOAc) Rf 0.40; HPLC ES-MS m/z (rel abundance) 379 (MH+, 100%).

Workup

  1. temperatureto cool to room temperature
  2. additionpoured onto ice water
  3. extractionThe basic mixture was extracted with EtOAc
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash chromatography (EtOAc)

Sources & evidence

ORD record
ord-abd23e23f9b84149ae94b753c42620e8
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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