Reaktion #71703

Reaktionsgleichung

(2S)-4-{[2-bromo-4-(trifluoromethyl)phenyl]sulfonyl}-2-methyl-1-[(6-methyl-3-pyridinyl)carbonyl]piperazine

potassium carbonate

HCl

trimethylboroxin

→

title compound

(2S)-2-methyl-1-[(6-methyl-3-pyridinyl)carbonyl]-4-{[2-methyl-4-(trifluoromethyl)phenyl]sulfonyl}piperazine hydrochloride

Lösungsmittel

1,4-dioxane

DCM

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was concentrated under vacuum
2. 2
   workup.DISSOLUTIONdissolved in MeOH
3. 3
   Filtrationfiltered through a 5 g SCX column
4. 4
   workup.DISSOLUTIONanother small impurity so the product was dissolved in EtOAc (40 ml)
5. 5
   Extraktionextracted with HCl 2N (40 ml)
6. 6
   workup.ADDITION2 N NaOH was added to the aqueous layer until pH12 and product
7. 7
   Extraktionextracted with EtOAc (100 ml)
8. 8
   SonstigeThe organic phase was dried on a phase separation cartridge
9. 9
   Einengenconcentrated under vacuum
10. 10
    Extraktionso was extracted again with 2 N HCl (40 ml)
11. 11
    workup.ADDITION2 N NaOH was added to the aqueous layer until pH12 and product
12. 12
    Extraktionextracted with EtOAc (100 ml)
13. 13
    SonstigeThe organic layer was dried on a phase separation cartridge
14. 14
    Einengenconcentrated under vacuum
15. 15
    Sonstigeto give the free base of the product
16. 16
    Sonstigethe solvent was evaporated

Vorschrift

(2S)-4-{[2-bromo-4-(trifluoromethyl)phenyl]sulfonyl}-2-methyl-1-[(6-methyl-3-pyridinyl)carbonyl]piperazine (may be prepared as described in Description 31) (216 mg, 0.427 mmol), potassium carbonate (153 mg, 1.109 mmol) in 1,4-dioxane (9 ml) were stirred for 5 min then trimethylboroxin (0.154 ml, 1.109 mmol) and Pd(PPh3)4 (84 mg, 0.073 mmol) were added and the reaction mixture heated at 100° C. for 1 h. The reaction mixture was concentrated under vacuum, dissolved in MeOH and filtered through a 5 g SCX column. LCMS showed still some triphenylphosphine oxide and another small impurity so the product was dissolved in EtOAc (40 ml) and extracted with HCl 2N (40 ml). 2 N NaOH was added to the aqueous layer until pH12 and product extracted with EtOAc (100 ml). The organic phase was dried on a phase separation cartridge and concentrated under vacuum. LCMS of the first EtOAc layer showed it contained some of the product so was extracted again with 2 N HCl (40 ml). 2 N NaOH was added to the aqueous layer until pH12 and product extracted with EtOAc (100 ml). The organic layer was dried on a phase separation cartridge and the two batches were combined and concentrated under vacuum to give the free base of the product. The product was suspended in DCM, 0.5 ml of 1N HCl in ether was added and the solvent was evaporated to give the title compound (193 mg).

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