Benzoic acid, 3-mercapto- → 3-[5-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-pyridin-2-ylsulfanyl]-benzoic acid

HRID 2267027Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2267027
[SH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].Cl[C:12]1[N:17]=[CH:16][C:15]([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:28])[CH3:27])=[C:22]([OH:29])[C:21]=2[CH2:30][CH2:31][CH3:32])=[CH:14][CH:13]=1>CN(C)C=O.C(OCC)(=O)C>[C:26]([C:23]1[CH:24]=[CH:25][C:20]([O:19][CH2:18][C:15]2[CH:14]=[CH:13][C:12]([S:1][C:2]3[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=3)[C:5]([OH:7])=[O:6])=[N:17][CH:16]=2)=[C:21]([CH2:30][CH2:31][CH3:32])[C:22]=1[OH:29])(=[O:28])[CH3:27]

Komponenten

5

Edukt 2

HCID 95737Benzoic acid, 3-mercapto-HCID 866198471-[4-(6-Chloro-pyridin-3-ylmethoxy)-2-hydroxy-3-propyl-phenyl]-ethanone

Produkt 1

HCID 595994953-[5-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-pyridin-2-ylsulfanyl]-benzoic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Dissolve 3-mercapto-benzoic acid (482 mg, 3.13 mmol, commercially available) in dimethylformamide (20 mL) at 0° C. Add washed sodium hydride (300 mg), and stir the mixture for 10 minutes. Add 1-[4-(6-chloro-pyridin-3-ylmethoxy)-2-hydroxy-3-propyl-phenyl]-ethanone (1.00 g, 3.13 mmol). Stir the mixture at room temperature for 2 hours; then stir at 65° C. for 2 hours and finally stir at 120° C. overnight. Dilute in ethyl acetate, and wash with water twice. Extract the organic layer with saturated aqueous sodium bicarbonate. Acidify the aqueous layer with 2N hydrochloric acid hydrochloric acid to pH 3. Extract with ethyl acetate, wash with brine, dry and concentrate to afford 620 mg of a crude red solid. Purify the residue via chromatography, eluting with 1:1 hexane:ethyl acetate to afford the title compound as a light yellow powder (120 mg): 1H NMR (DMSO-d6) δ 0.84 (s, 3H), 1.44 (sextet, 2H), 2.55 (t, 2H), 2.58 (s, 3H), 5.24 (s, 2H), 6.74 (d, 1H), 7.14 (d, 1H), 7.63 (t, 1H), 7.75 (d, 1H), 7.81-7.84 (m, 2H), 8.02 (d, 1H), 8.05 (s, 1H), 8.51 (s, 1H), 12.84 (s, 1H), 13.21 (bs, 1H); MS (APCI-neg mode) m/z (rel intensity) 436 (100).

Aufarbeitung

  1. customat 0° C
  2. additionAdd
  3. washwashed sodium hydride (300 mg)
  4. stirringStir the mixture at room temperature for 2 hours
  5. stirringthen stir at 65° C. for 2 hours
  6. stirringfinally stir at 120° C. overnight
  7. washwash with water twice
  8. extractionExtract the organic layer with saturated aqueous sodium bicarbonate
  9. extractionExtract with ethyl acetate
  10. washwash with brine
  11. customdry
  12. concentrationconcentrate
  13. customto afford 620 mg of a crude red solid
  14. customPurify the residue via chromatography
  15. washeluting with 1:1 hexane

Quellen und Nachweise

ORD-Eintrag
ord-2af4db11eaac4542bb6aa19030f2172a
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07858646B2

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