Potassium Phosphate, Tribasic → 5-(4-Hydroxy-piperidin-1-yl)-biphenyl-2-carboxylic acid methyl ester

HRID 1689768Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1689768
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)=[CH:6][C:5]=1Br.[C:19]1(B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:4]1[C:5]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)=[CH:8][CH:9]=1)=[O:18]

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 669064532-Bromo-4-(4-hydroxy-piperidin-1-yl)-benzoic acid methyl ester

Produkt 1

HCID 669063285-(4-Hydroxy-piperidin-1-yl)-biphenyl-2-carboxylic acid methyl esterAusbeute 92 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 2-bromo-4-(4-hydroxy-piperidin-1-yl)-benzoic acid methyl ester (1.2 g, 3.82 mmol), phenylboronic acid (800 mg; 6.56 mmol), potassium phosphate, tribasic, mono-hydrate (1.3 g, 10.7 mmol), and tetrakis(triphenylphosphine)palladium (500 mg, 0.433 mmol) in 1,2-dimethoxyethane (25 mL) and water (1 mL) is heated to 90° C. under a nitrogen atmosphere for 24 h. The mixture is concentrated and partitioned between ethyl acetate and water. The solvent layers are separated and the aqueous layer is extracted with ethyl acetate (3×). The combined ethyl acetate layers are dried (MgSO4), filtered, and concentrated under reduced pressure. The residue is purified on silica (120 g) eluting with a gradient of 0% to 100% ethyl acetate in heptane to provide the desired product (1.09 g, 92%) as a gummy residue. LC-ES/MS m/z 312.0 (M+1)

Aufarbeitung

  1. concentrationThe mixture is concentrated
  2. custompartitioned between ethyl acetate and water
  3. customThe solvent layers are separated
  4. extractionthe aqueous layer is extracted with ethyl acetate (3×)
  5. dry with materialThe combined ethyl acetate layers are dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified on silica (120 g)
  9. washeluting with a gradient of 0% to 100% ethyl acetate in heptane

Quellen und Nachweise

ORD-Eintrag
ord-f9ea7e08183f46bbb506ea5e594752a3
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153624B2

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