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

HRID 2110889ノート

反応式

HRID 2110889 の反応式
[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]

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-7c0b70abcf7e4022b44a9e3a1a22f8ab
出典データセット
uspto-grants-2009_04
特許番号
US07517910B2

反応ノート

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