Reaktion #1115199

Reaktionsgleichung

(R)-6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-pyridine-3-sulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide

bis(pinacolato)diboron

potassium acetate

→

(R)-6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-pyridine-3-sulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide

Ausbeute 84.0%

Lösungsmittel

dioxane

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was then cooled to room temperature
2. 2
   Filtrationfiltered through a silica-celite pad
3. 3
   EinengenThe filtrate was concentrated
4. 4
   workup.DISSOLUTIONdissolved in acetone (10 mL)
5. 5
   Temperaturcooled to 0° C
6. 6
   workup.ADDITIONInto this solution was added an aqueous solution of Oxone (10 mL, 1.0 M)
7. 7
   workup.STIRRINGThe mixture was stirred at room temperature for 15 min
8. 8
   workup.ADDITIONdiluted with ethyl acetate and water
9. 9
   ExtraktionThe aqueous layer was extracted with ethyl acetate
10. 10
    ExtraktionThe organic extractions
11. 11
    Waschenwashed with aq. NaHSO3 and brine
12. 12
    Trocknendried over Na2SO4
13. 13
    Einengenconcentrated
14. 14
    SonstigePurification on silica gel eluting with 40% ethyl acetate in hexane

Vorschrift

A mixture of (R)-6-(5-bromo-3-cyano-1-cyclopentyl-6-methyl-1H-indol-2-yl)-pyridine-3-sulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide (0.54 g, 0.97 mmol), bis(pinacolato)diboron (0.5 g, 2.0 mmol), PdCl2dppf-CH2Cl2 complex (16 mg, 0.02 mmol) and potassium acetate (0.40 g, 4.0 mmol) in dioxane (5 mL) was stirred at 80° C. overnight. The mixture was then cooled to room temperature, diluted with ethyl acetate and filtered through a silica-celite pad. The filtrate was concentrated, dissolved in acetone (10 mL) and cooled to 0° C. Into this solution was added an aqueous solution of Oxone (10 mL, 1.0 M). The mixture was stirred at room temperature for 15 min and diluted with ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The organic extractions were combined and washed with aq. NaHSO3 and brine, dried over Na2SO4, and concentrated. Purification on silica gel eluting with 40% ethyl acetate in hexane gave (R)-6-(3-cyano-1-cyclopentyl-5-hydroxy-6-methyl-1H-indol-2-yl)-pyridine-3-sulfonic acid (2,2,2-trifluoro-1-methyl-ethyl)-amide as a yellow solid (0.40 g, 84%); Melting point: 239-240° C.; MS m/z 493.2 M+H+; 1H NMR (500 MHz, CD3COCD3) δ 9.24 (dd, J=2.30, 0.65 Hz, 1H), 8.50 (dd, J=8.25, 2.35 Hz, 1H), 8.42 (s, 1H), 8.10 (dd, J=8.25, 0.85 Hz, 1H), 7.47 (bs, 1H), 7.54 (s, 1H), 7.15 (s, 1H), 5.30-5.26 (m, 1H), 4.40-4.35 (m, 1H), 2.40 (s, 3H), 2.34-2.31 (m, 2H), 2.16-2.14 (m, 2H), 2.10-2.07 (m, 2H), 1.74-1.72 (m, 2H), 1.21 (d, J=2.25 Hz, 3H).

Quelle