Hydrochloric Acid → 2-methyl-2-{[1-(1,2,3,4-tetrahydronaphth-1-yl)-1H-indazol-3-yl]methoxy}-propanoic acid

HRID 2074527

Reaktionsgleichung

Reaktionsgleichung von HRID 2074527
[CH3:1][C:2]([O:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][N:10]=1)([CH3:6])[C:3]([OH:5])=[O:4].[H-].[Na+].Cl[CH:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23][CH2:22]1.Cl.[OH-].[Na+]>CN(C=O)C.C(O)C.O>[CH3:6][C:2]([O:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([CH:29]2[C:30]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:26][CH2:27][CH2:28]2)[N:10]=1)([CH3:1])[C:3]([OH:5])=[O:4]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 1887171-Chloro-1,2,3,4-tetrahydronaphthaleneHCID 178459030HCID 178459030, Verbindung

Produkt 1

HCID 442171642-methyl-2-{[1-(1,2,3,4-tetrahydronaphth-1-yl)-1H-indazol-3-yl]methoxy}-propanoic acidAusbeute 91,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 2-methyl-2-[(1H-indazol-3-yl)methoxy]propanoic acid (26 g; 0.093 mol) in DMF (200 ml) was added 60% NaH (10 g; 0.25 mol) and the mixture was stirred for 10 minutes at 60° C. 1-chloro-1,2,3,4-tetrahydronaphthalene (0.217 mol) was then added to the mixture and the whole was stirred at 60° C. for 18 hours. The reaction was stopped by pouring the mixture into water (1 L), followed by acidifying with 5 N HCl and extracting the product with diethyl ether (3×250 ml). The residue obtained was dissolved in 95° ethanol (100 ml) and treated at reflux with 1N NaOH (200 ml) for 2 hours. The solution was then cooled to room temperature and washed with diethyl ether (3×200 ml). The alkaline phase was then acidified with concentrated HCl and extracted with ethyl acetate (3×300 ml). The combined organic phases were concentrated under reduced pressure and the crude residue obtained was purified by crystallization from ethyl acetate. 31 g of 2-methyl-2-{[1-(1,2,3,4-tetrahydronaphth-1-yl)-1H-indazol-3-yl]methoxy}-propanoic acid were thus obtained.

Aufarbeitung

  1. stirringthe whole was stirred at 60° C. for 18 hours
  2. extractionextracting the product with diethyl ether (3×250 ml)
  3. customThe residue obtained
  4. additiontreated
  5. temperatureThe solution was then cooled to room temperature
  6. washwashed with diethyl ether (3×200 ml)
  7. extractionextracted with ethyl acetate (3×300 ml)
  8. concentrationThe combined organic phases were concentrated under reduced pressure
  9. customthe crude residue obtained
  10. customwas purified by crystallization from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-680e65cc00894bbcb9ddf79fe8ab4ce1
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919518B2

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