Tributylphosphine → 3-[2-fluoro-4-({4-[(2-phenyl-1H-indol-1-yl)methyl]benzyl}oxy)phenyl]propanoic acid

HRID 2110889노트

반응식

HRID 2110889 반응식
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([O:13]CC)=[O:12].[C:16]1([C:22]2[N:23]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([CH2:38]O)=[CH:34][CH:33]=3)[C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[OH-].[Na+]>C(OCC)(=O)C.O1CCCC1.CO.C(OCC)C>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:38][C:35]2[CH:34]=[CH:33][C:32]([CH2:31][N:23]3[C:24]4[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:30]=[C:22]3[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:37][CH:36]=2)[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([OH:13])=[O:12]

참가 물질

10

반응물 5

HCID 13831TributylphosphineHCID 14798Sodium HydroxideHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 23082888Ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoateHCID 23111705{4-[(2-phenyl-1H-indol-1-yl)methyl]phenyl}methanol

생성물 1

HCID 115981523-[2-fluoro-4-({4-[(2-phenyl-1H-indol-1-yl)methyl]benzyl}oxy)phenyl]propanoic acid수율 79%

시약·촉매·용매 4

HCID 887Methanol용매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

To a mixture of ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (0.29 g, 1.34 mmol), {4-[(2-phenyl-1H-indol-1-yl)methyl]phenyl}methanol (0.38 g, 1.22 mmol), tributylphosphine (0.46 mL, 1.83 mmol) and tetrahydrofuran (7.6 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.46 g, 1.83 mmol) with stirring at 0° C., and the mixture was stirred at room temperature for 18 hr. Diethyl ether was added to the reaction mixture. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1) to give a colorless oil. Then, a mixture of the obtained oil, 1 N aqueous sodium hydroxide solution (2.5 mL), methanol (5.0 mL) and tetrahydrofuran (10.0 mL) was stirred at room temperature for 14 hr. The reaction mixture was diluted with ethyl acetate, and the mixture washed with 1 N hydrochloric acid, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=1/2) to give the title compound (0.46 g, yield 79%) as colorless crystals. MS (APCI−): 478 (M−H), 1H NMR (CDCl3) δ: 2.64 (2H, t, J=7.8 Hz), 2.91 (2H, t, J=7.8 Hz), 4.96 (2H, s), 5.38 (2H, s), 6.61-6.70 (3H, m), 7.01-7.20 (6H, m), 7.32 (2H, d, J=8.1 Hz), 7.34-7.47 (5H, m), 7.67 (1H, m).

후처리

  1. stirringthe mixture was stirred at room temperature for 18 hr
  2. filtrationThe insoluble material was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1)
  5. customto give a colorless oil
  6. stirringwas stirred at room temperature for 14 hr
  7. washthe mixture washed with 1 N hydrochloric acid, water and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=1/2)

출처 및 근거

ORD 기록
ord-7c0b70abcf7e4022b44a9e3a1a22f8ab
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07517910B2

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