4-Phenyl-2-pyrrolidinone → 1-{[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-phenylpyrrolidin-2-one

HRID 1028525

반응식

HRID 1028525 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:11]1([CH:17]2[CH2:21][NH:20][C:19](=[O:22])[CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Br[CH2:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=1[C:35]1[CH:40]=[C:39]([CH:41]([CH3:43])[CH3:42])[CH:38]=[CH:37][C:36]=1[O:44][CH3:45]>C1COCC1>[CH:41]([C:39]1[CH:38]=[CH:37][C:36]([O:44][CH3:45])=[C:35]([C:26]2[CH:27]=[CH:28][C:29]([C:31]([F:34])([F:32])[F:33])=[CH:30][C:25]=2[CH2:24][N:20]2[CH2:21][CH:17]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:18][C:19]2=[O:22])[CH:40]=1)([CH3:43])[CH3:42]

참가 물질

5

반응물 3

HCID 1213974-Phenyl-2-pyrrolidinoneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 533636432-(Bromomethyl)-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl

생성물 1

HCID 117054191-{[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-phenylpyrrolidin-2-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

Sodium bis(trimethylsilyl)amide (114 μL of a 1M solution in THF, 0.114 mmol) was added to a stirred solution of 4-phenylpyrrolidin-2-one (Winans, C. F., Adkins, H., J. Am. Chem. Soc., 1933, 55, 4167-4176) (17 mg, 0.103 mmol) in dry THF (1 mL) at room temperature under N2. The reaction was stirred for 5 min and a solution of 2-(bromomethyl)-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl (20 mg, 0.0516 mmol) in dry THF (2 mL) was added by cannula. The reaction was stirred at room temperature for 3 days. The reaction was quenched with saturated NH4Cl (10 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-90% EtOAc in hexanes gradient) to afford 1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-phenylpyrrolidin-2-one as a colorless oil. Rf=0.11 (20% EtOAc/hexanes). LCMS calc.=468.22; found=468.2 (M+1)+. 1H NMR (600 MHz, benzene-d6, 1:1 mixture of atropisomers) δ 7.79 (s, 0.5H), 7.73 (s, 0.5H), 7.33 (d, J=7.7 Hz, 1H), 7.08-7.04 (m, 4H), 6.99 (m, 1H), 6.92 (s, 0.5H), 6.88 (s, 0.5H), 6.76 (dd, J=16.0, 7.4 Hz, 2H), 6.60 (dd, J=8.5, 3.1 Hz, 1H), 4.58 (d, J=15.4 Hz, 1H), 4.38 (t, J=13.9 Hz, 1H), 3.29 (s, 1.5H), 3.26 (s, 1.5H), 2.85-2.73 (m, 3H), 2.63-2.57 (m, 1H), 2.38-2.28 (m, 1H), 2.21-2.11 (m, 1H), 1.20-1.16 (m, 6H).

후처리

  1. stirringThe reaction was stirred at room temperature for 3 days
  2. customThe reaction was quenched with saturated NH4Cl (10 mL)
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic extracts were washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto give the crude product
  8. customThis was purified by flash chromatography (Si, 12×160 mm, 0-90% EtOAc in hexanes gradient)

출처 및 근거

ORD 기록
ord-0dc2da0df43748a6834c81622b3aa3a4
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735435B2

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