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

HRID 1838006노트

반응식

HRID 1838006 반응식
C([BH-](CC)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]1C1C=CC=CC=1)=[O:32].[C:46]1([C:52]2[S:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[Li]CCCC.N1CCCC1=O.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[OH:13][C@H:14]([C:54]1[S:53][C:52]([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)=[CH:56][CH:55]=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]([OH:32])=[CH:26][CH:27]=1

참가 물질

10

반응물 7

HCID 120252-PyrrolidoneHCID 699992-PhenylthiopheneHCID 2724141Tetrabutylammonium FluorideHCID 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 178418339Butyllithium

생성물 1

HCID 10271085(+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-hydroxy-phenyl)-1-methylpyrrolidin-2-one수율 82%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

Intermediate Y 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 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. The resulting product, (±)-(4R*,5R*)-5[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-1-methyl-4-[4-tert-butyldimethylsilyloxy)phenyl]pyrrolidin-2-one (0.050 g, 0.10 mmol), was dissolved in THF (1 mL) under Ar, a solution of TBAF (1M in THF, 0.11 mL, 0.11 mmol) was added, and the resulting solution was stirred for 4 min. The reaction was treated with water and a saturated NH4Cl solution, then extracted with EtOAc. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (EtOAc) to yield (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-hydroxy-phenyl)-1-methylpyrrolidin-2-one (31 mg, 82%) as a white powder: mp 248-249° C.; TLC (EtOAc) Rf 0.37.

후처리

  1. extractiona saturated NH4Cl solution, then extracted with EtOAc
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by flash chromatography (EtOAc)

출처 및 근거

ORD 기록
ord-b051b5e042ad4ce395e355c926caf709
출처 데이터셋
uspto-grants-2004_08
특허 번호
US06784167B2

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