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Dimethylformamide → 3-[4-[2-(2-Biphenyl-4-yl-5-methyloxazol-4-yl)ethoxy]-2-(4-trifluoromethylphenoxy-methyl)-phenyl]-propionic acid

HRID 1181127
ノート
印刷プレビュー

反応式

HRID 1181127 の反応式
C(OC(=O)C[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)(C)(C)C.[C:29]1([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH:34]=[CH:33][C:32]([C:35]2[O:36][C:37]([CH3:53])=[C:38]([CH2:40][CH2:41]OS(C3C=CC(C)=CC=3)(=O)=O)[N:39]=2)=[CH:31][CH:30]=1.[CH3:60]N(C=O)C.[C:65](=[O:68])([O-])[O-:66].[Cs+].[Cs+]>CCOCC>[C:29]1([C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:34]=[CH:33][C:32]([C:35]2[O:36][C:37]([CH3:53])=[C:38]([CH2:40][CH2:41][O:15][C:12]3[CH:13]=[CH:14][C:9]([CH2:8][CH2:60][C:65]([OH:66])=[O:68])=[C:10]([CH2:16][O:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:25])([F:27])[F:26])=[CH:20][CH:19]=4)[CH:11]=3)[N:39]=2)=[CH:31][CH:30]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 12966835Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl esterHCID 589790123-[4-Hydroxy-2-(4-trifluoromethylphenoxymethyl)phenyl]propionic acid tert-butyl ester

生成物 1

HCID 102822133-[4-[2-(2-Biphenyl-4-yl-5-methyloxazol-4-yl)ethoxy]-2-(4-trifluoromethylphenoxy-methyl)-phenyl]-propionic acid
収率 71%

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

実験手順

General procedure for parallel synthesis using, the DynaVac Carousel apparatus: A 50 mL glass tube with screw cap and nitrogen inlet was charged with 3-[4-hydroxy-2-(4-trifluoromethylphenoxymethyl)phenyl]propionic acid tert-butyl ester (0.050 g, 0.146 mmol), toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-5-methyloxazol-4-yl)ethyl ester (0.078 g, 0.18 mmol), anhydrous DMF (0.5 mL), and then cesium carbonate (0.072 g, 0.22 mmol). The mixture was stirred at ambient temperature for 16 h. MS analysis of the reaction indicated formation of the ester intermediate MS (ES) m/e 658 (M+1). The reaction mixture was poured into ether (30 mL). The organic layer was washed with brine (2×), dried (Na2SO4), and concentrated. The crude residue was diluted with CH2Cl2 (2 mL) and then trifluoroacetic acid (1 mL). The mixture was stirred at ambient temperature for 2 h and concentrated under a stream of N2. The crude product was purified by mass-directed reverse phase HPLC to provide the title compound (0.053 g, 71%). 1H NMR (250 MHz, CDCl3) 2.41 (s, 3H), 2.70 (t, J=7.7 Hz, 2H), 2.95-3.05 (m, 4H), 4.28 (t, J=6.6 Hz, 2H), 5.09 (s, 2H), 6.90 (dd, J=8.5, 2.8 Hz, 1H), 7.01 (d, J=2.6 Hz, 1H), 7.06 (d, J=8.6 Hz, 2H), 7.21 (d, J=8.5 Hz, 1H), 7.41-7.72 (m, 9H), 8.07 (d, J=8.4 Hz, 2H). MS (ES) m/e 602 (M+1).

後処理

  1. customGeneral procedure for parallel synthesis
  2. customthe DynaVac Carousel apparatus: A 50 mL glass tube with screw cap
  3. washThe organic layer was washed with brine (2×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. additionThe crude residue was diluted with CH2Cl2 (2 mL)
  7. stirringThe mixture was stirred at ambient temperature for 2 h
  8. concentrationconcentrated under a stream of N2
  9. customThe crude product was purified by mass-directed reverse phase HPLC

出典と根拠

ORDレコード
ord-591f638edf294b809daaa6080272aee0
出典データセット
uspto-grants-2007_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07282501B2

反応ノート

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