Hydrochloric Acid → 1-[2-hydroxy-4-(4-{hydroxy-[3-(2H-tetrazol-5-yl)-phenyl]-methyl}-benzyloxy)-3-propyl-phenyl]-ethanone

HRID 1161029

Reaktionsgleichung

Reaktionsgleichung von HRID 1161029
[C:1]([C:4]1[CH:33]=[CH:32][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([O:25]C3CCCCO3)[C:17]3[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=3)[C:20]#[N:21])=[CH:12][CH:11]=2)=[C:6]([CH2:34][CH2:35][CH3:36])[C:5]=1[OH:37])(=[O:3])[CH3:2].[N-:38]=[N+:39]=[N-:40].[Na+].Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.[Br-].[Zn+2].[Br-].C(O)(C)C>[OH:37][C:5]1[C:6]([CH2:34][CH2:35][CH3:36])=[C:7]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([CH:16]([OH:25])[C:17]3[CH:24]=[CH:23][CH:22]=[C:19]([C:20]4[N:38]=[N:39][NH:40][N:21]=4)[CH:18]=3)=[CH:14][CH:15]=2)[CH:32]=[CH:33][C:4]=1[C:1](=[O:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 33557Sodium AzideHCID 521998p-Toluenesulfonic acid monohydrateHCID 666996043-[[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile

Produkt 1

HCID 116625471-[2-hydroxy-4-(4-{hydroxy-[3-(2H-tetrazol-5-yl)-phenyl]-methyl}-benzyloxy)-3-propyl-phenyl]-ethanoneAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 10421208Zinc bromideKatalysatorHCID 962WaterLösungsmittel2×HCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

Bring to a heavy reflux, a mixture of 3-[[4-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (3.0 g, 6 mmol), zinc (II) bromide (4.1 g, 18 mmol), sodium azide (2.34 g, 36 mmol), water (20 mL) and isopropyl alcohol (20 mL) for 18 hours. Cool and dilute the reaction mixture with water (100 mL) and adjust the pH to 2 with 1M hydrochloric acid. Extract the product with ethyl acetate (2×150 mL), combine the extracts and wash with water (100 mL), brine (100 mL), dry over magnesium sulfate, filter, and concentrate. Stir the residue in methanol (50 mL), and add p-toluenesulfonic acid mono hydrate (4 g, 21 mmol) and stir at room temperature for an hour. Concentrate the mixture and dilute with water (100 mL). Extract the product with ethyl acetate (2×100 mL). Wash the combined extracts with water (2×100 mL), brine (100 mL), dry over magnesium sulfate, filter, and concentrate. Purify the resulting residue via silica chromatography eluting with 1:1 hexanes:ethyl acetate to 1:1 ethyl acetate:acetone to acetone to give the title compound (2.6 g, 95%) as a tan solid. 1H NMR (DMSO-d6) d 12.86 (s, 1H), 8.12 (s, 1H), 7.87 (d, 1H), 7.80 (d, 1H), 7.39-7.55 (m, 6H), 6.72 (d, 1H), 6.11 (d, 1H), 5.82 (d, 1H), 5.23 (s, 2H), 2.56 (s, 3H), 2.57-2.60 (m, 2H), 1.44-1.52 (m, 2H), 0.87 (t, 3H). LCMS (m/z) 457 M−1.

Aufarbeitung

  1. temperatureCool
  2. extractionExtract the product with ethyl acetate (2×150 mL)
  3. washwash with water (100 mL), brine (100 mL)
  4. dry with materialdry over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. stirringstir at room temperature for an hour
  8. concentrationConcentrate the mixture
  9. additiondilute with water (100 mL)
  10. extractionExtract the product with ethyl acetate (2×100 mL)
  11. washWash the combined extracts with water (2×100 mL), brine (100 mL)
  12. dry with materialdry over magnesium sulfate
  13. filtrationfilter
  14. concentrationconcentrate
  15. customPurify the resulting residue via silica chromatography
  16. washeluting with 1:1 hexanes

Quellen und Nachweise

ORD-Eintrag
ord-98c286e76c634bd693fa37182ac1467e
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07816523B2

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