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

HRID 1838003노트

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HRID 1838003 반응식
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

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
70 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-abd23e23f9b84149ae94b753c42620e8
출처 데이터셋
uspto-grants-2004_08
특허 번호
US06784167B2

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