Hydrochloric Acid → 3-{[4-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-fluoro-methyl}-benzoic acid

HRID 1717754

Reaktionsgleichung

Reaktionsgleichung von HRID 1717754
[C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16](O)[C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2].ClCCl.CN(S(F)(F)[F:38])C.Cl>[OH-].[Na+].O1CCCC1>[C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([F:38])[C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 123203Sulfur, trifluoro(N-methylmethanaminato)-2×HCID 666995643-{[4-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzoic acid

Produkt 1

HCID 578843923-{[4-(4-Acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-fluoro-methyl}-benzoic acidAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A suspension of 3-{[4-(4-acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzoic acid (100 mg, 0.246 mmol) and dichloromethane (5 mL) is stirred at −78° C. Dimethylamino sulfur trifluoride (35 μL, 0.271 mmol) is added and the mixture is warmed to room temperature. An additional portion of dimethylamino sulfur trifluoride (35 μL, 0.271 mmol) is added and suspension becomes a solution. The reaction mixture is diluted with aqueous 2N sodium hydroxide (5 mL) and tetrahydrofuran (2 mL) and stirred 10 min. The pH is adjusted to 2 with aqueous 5N hydrochloric acid and extracted with ethyl acetate (2×20 mL). The combined extracts are concentrated and the resulting residue is purified via silica chromatography eluting with hexanes to 1:1 hexanes:ethyl acetate to give the title compound (70 mg, 70%) as a white solid. 1H NMR (DMSO-d6) δ 13.12 (s, 1H), 12.86 (s, 1H), 7.93-7.95 (m, 2H), 7.82 (d, 1H), 7.68 (d, 1H), 7.44-7.59 (m, 5H), 6.75-6.90 (d, 1H), 6.72 (d, 1H), 5.29 (s, 2H), 2.59 (s, 3H), 2.06 (s, 3H). LCMS M−1 407.

Aufarbeitung

  1. temperaturethe mixture is warmed to room temperature
  2. stirringstirred 10 min
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. concentrationThe combined extracts are concentrated
  5. customthe resulting residue is purified via silica chromatography
  6. washeluting with hexanes to 1:1 hexanes

Quellen und Nachweise

ORD-Eintrag
ord-950bbb52e5ae449b8fd183cd9fe8291e
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07803938B2

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