Reaktion #1523394

Reaktionsgleichung

4-chlorobenzyl bromide

acid

(+/−)-(5-bromo-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid

diazomethane

NaH

→

title compound

Ausbeute 78.9%

(+/−)-[5-bromo-4-(4-chlorobenzyl)-7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]-indol-3-yl]acetic acid

Ausbeute 78.9%

Lösungsmittel

THF

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeexcess until complete consumption of the acid
2. 2
   SonstigeThen, the solvents were removed under vacuum
3. 3
   SonstigeTo a solution of the crude methyl ester thus formed in 20 mL of DMF
4. 4
   Temperaturcooled again to −78° C.
5. 5
   workup.WAITAfter 5 min
6. 6
   Temperaturthe temperature was warmed to 0° C.
7. 7
   workup.STIRRINGthe mixture was stirred for 20 min
8. 8
   SonstigeAt this time, the reaction was quenched by the addition of 2 mL of AcOH
9. 9
   workup.ADDITIONthis mixture was poured into a separatory funnel
10. 10
    workup.ADDITIONcontaining 1N HCl/EtOAc
11. 11
    SonstigeThe layers were separated
12. 12
    Waschenthe organic layer was washed with brine
13. 13
    Trocknendried over anhydrous Na2SO4
14. 14
    Einengenconcentrated
15. 15
    SonstigeThe crude material was further purified by trituration with EtOAc/hexanes

Vorschrift

To a solution of 2.13 g of the acid from Step 3 in 10 mL of THF, a solution of diazomethane in ether was added in excess until complete consumption of the acid as monitored on TLC. Then, the solvents were removed under vacuum. To a solution of the crude methyl ester thus formed in 20 mL of DMF, 539 mg of a NaH suspension (60% in oil) was added at −78° C. The suspension was stirred for 10 min at 0° C., cooled again to −78° C. and treated with 1.70 g of 4-chlorobenzyl bromide. After 5 min, the temperature was warmed to 0° C. and the mixture was stirred for 20 min. At this time, the reaction was quenched by the addition of 2 mL of AcOH and this mixture was poured into a separatory funnel containing 1N HCl/EtOAc. The layers were separated and the organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated. The alkylated material was hydrolyzed using the procedure described in Step 2. The crude material was further purified by trituration with EtOAc/hexanes to yield 2.35 g of the title compound as a pale brown solid.

Quelle