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Hydrochloric Acid → 7-(2-Methoxyphenyl)-3-(3-((2-methyl-1-naphthyl)oxy)propyl)-1h-indole-2-carboxylic acid

HRID 2095242
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2095242
O[CH2:2][CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH3:21])[CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:22]([O:24]CC)=[O:23].[CH3:27][C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]=1[OH:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Li+].[OH-].Cl>C1COCC1.O.CO>[CH3:21][O:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:8]=1[NH:7][C:6]([C:22]([OH:24])=[O:23])=[C:5]2[CH2:4][CH2:3][CH2:2][O:38][C:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:36]=[CH:37][C:28]=1[CH3:27]
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Komponenten

10

Edukt 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11776TriphenylphosphineHCID 240552-Methyl-1-naphtholHCID 97268Di-tert-butyl azodicarboxylateHCID 68940496ethyl 3-(3-hydroxypropyl)-7-(2-methoxyphenyl)-1H-indole-2-carboxylate

Produkt 1

HCID 25145597
7-(2-Methoxyphenyl)-3-(3-((2-methyl-1-naphthyl)oxy)propyl)-1h-indole-2-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a mixture of EXAMPLE 47A (71 mg), 2-methyl-1-naphthol (35 mg), triphenylphosphine (58 mg) in THF (2 mL) and di-tert-butyl azodicarboxylate (55 mg) was stirred at ambient temperature overnight and partitioned between ethyl acetate (150 mL) and water (50 mL). The organic layer was washed with brine and a dried (Na2SO4), filtered and concentrated. The concentrate was purified by flash chromatography on silica gel with 5% ethyl acetate in hexanes to provide an intermediate which was dissolved in THF (2 mL), methanol (1 mL) and water (1 mL) and hydrolyzed with LiOH (100 mg) overnight. The mixture was acidified with 5% HCl and extracted with ethyl acetate. The extract was washed with water and brine and dried (Na2SO4), filtered and concentrated. The concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA). 1H NMR (300 MHz, CDCl3) δ 8.74 (s, 1H), 8.12 (dd, 1H), 7.82 (d, 1H), 7.77 (d, 1H), 7.52 (d, 1H), 7.36-7.47 (m, 5H), 7.27 (d, 1H), 7.09 (t, 2H), 4.10 (t, 2H), 3.83 (s, 3H), 3.48 (t, 2H), 2.46 (s, 3H), 2.38 (m, 2H).

Aufarbeitung

  1. custompartitioned between ethyl acetate (150 mL) and water (50 mL)
  2. washThe organic layer was washed with brine
  3. dry with materiala dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe concentrate was purified by flash chromatography on silica gel with 5% ethyl acetate in hexanes
  7. customto provide an intermediate which
  8. extractionextracted with ethyl acetate
  9. washThe extract was washed with water and brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-47994b705d19407c9a687d7bcaded658
Quelldatensatz
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08445679B2

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