Reaktion #1523397

Reaktionsgleichung

HCl

ester

(+/−)-Ethyl[8-Bromo-9-(4-chlorobenzyl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-1-yl]acetate

methanesulfinic acid sodium salt

NaOH

→

desired acid

Ausbeute 61.8%

(+/−)-[9-(4-Chlorobenzyl)-6-fluoro-8-methanesulfonyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl]acetic acid

Ausbeute 61.8%

Lösungsmittel

THF

methanol

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe resulting mixture was degassed under a flow of N2
2. 2
   TemperaturThe reaction mixture was cooled to room temperature
3. 3
   workup.ADDITIONdiluted with minimum amount of a 1:1 mixture of EtOAc/hexane
4. 4
   FiltrationThe resulting mixture was filtered through a pad of silica gel
5. 5
   Waschenfurther eluted with EtOAc
6. 6
   EinengenThe filtrate was concentrated to about 50 mL
7. 7
   Waschenwashed with water and brine
8. 8
   SonstigeThe organic phase was collected
9. 9
   Trocknendried over anhydrous sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Sonstigeevaporated
12. 12
    SonstigeThe residue was purified by flash chromatography over silica gel (30% EtOAc/hexane)
13. 13
    Sonstigeto afford 320 mg
14. 14
    Extraktionextracted with EtOAc
15. 15
    TrocknenThe separated organic phase was dried over anhydrous sodium sulfate
16. 16
    Filtrationfiltered
17. 17
    Sonstigeevaporated
18. 18
    TemperaturThe residue was refluxed with hexane
19. 19
    workup.STIRRINGunder rigorous stirring for 0.5 h
20. 20
    TemperaturThe resulting mixture was cooled to rt under rigorous stirring
21. 21
    Filtrationfiltered

Vorschrift

To a solution of 478 mg of the ester prepared in step 2 in 8 mL of NMP, 510 mg of methanesulfinic acid sodium salt and 950 mg of CuI (I) was added successively. The resulting mixture was degassed under a flow of N2, then heated at 140° C. for 8 h under rigorous stirring. The reaction mixture was cooled to room temperature, diluted with minimum amount of a 1:1 mixture of EtOAc/hexane. The resulting mixture was filtered through a pad of silica gel, further eluted with EtOAc. The filtrate was concentrated to about 50 mL, and washed with water and brine. The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was purified by flash chromatography over silica gel (30% EtOAc/hexane) to afford 320 mg of desired sulfonated material, which was dissolved in 5 mL of THF plus 5 mL of methanol. To the resulting solution, 5 mL of 2 N of NaOH was added and the resulting mixture was stirred at rt for 6 h. The reaction mixture was neutralized with 1 M HCl aqueous solution and extracted with EtOAc. The separated organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was refluxed with hexane under rigorous stirring for 0.5 h. The resulting mixture was cooled to rt under rigorous stirring, and filtered to afford 278 mg of desired acid.

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