Tributylphosphine → Methyl [(3S)-6-({3'-fluoro-2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate

HRID 416188ノート

反応式

HRID 416188 の反応式
[OH:1][C:2]1[CH:15]=[CH:14][C:5]2[C@H:6]([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH2:7][O:8][C:4]=2[CH:3]=1.[F:16][C:17]1[C:18]([CH3:40])=[C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38]O)[CH:33]=2)[C:20]([CH3:31])=[CH:21][C:22]=1[O:23][CH2:24][CH2:25][CH2:26][S:27]([CH3:30])(=[O:29])=[O:28].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>CCCCCC.O1CCCC1.C1(C)C=CC=CC=1>[CH3:13][O:12][C:10](=[O:11])[CH2:9][C@H:6]1[C:5]2[CH:14]=[CH:15][C:2]([O:1][CH2:38][C:34]3[CH:33]=[C:32]([C:19]4[C:20]([CH3:31])=[CH:21][C:22]([O:23][CH2:24][CH2:25][CH2:26][S:27]([CH3:30])(=[O:29])=[O:28])=[C:17]([F:16])[C:18]=4[CH3:40])[CH:37]=[CH:36][CH:35]=3)=[CH:3][C:4]=2[O:8][CH2:7]1

参加物

8

反応物 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 53393313(S)-Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateHCID 59342565{3'-Fluoro-2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methanol

生成物 1

HCID 59342579Methyl [(3S)-6-({3'-fluoro-2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate収率 77%

試薬・触媒・溶媒 3

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

実験手順

A solution of methyl [(3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetate (0.729 g, 3.50 mmol), {3′-fluoro-2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methanol (1.28 g, 3.50 mmol) and tributylphosphine (1.13 g, 5.60 mmol) in a mixed solvent of toluene (45 mL) and tetrahydrofuran (5 mL) was stirred, 1,1′-(azodicarbonyl)dipiperidine (1.41 g, 5.60 mmol) was added, and the mixture was stirred at room temperature for 4 hr under nitrogen atmosphere. Hexane (50 mL) was added to the reaction mixture, the precipitated insoluble substance was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=40:60-80:20) and basic silica gel column chromatography (ethyl acetate:hexane=40:60-100:0), and the obtained crystals were recrystallized from heptane-ethyl acetate to give the title compound (1.50 g, yield 77%) as colorless crystals.

後処理

  1. filtrationthe precipitated insoluble substance was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=40:60-80:20) and basic silica gel column chromatography (ethyl acetate:hexane=40:60-100:0)
  4. customthe obtained crystals were recrystallized from heptane-ethyl acetate

出典と根拠

ORDレコード
ord-052c6b8f0b7f433f98074e5123357150
出典データセット
uspto-grants-2012_01
特許番号
US08088821B2

反応ノート

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