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

Temperatur

100 °C

(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 1 N HCl in ether was added and the solvent was evaporated to give the title compound (193 mg).

1. concentrationThe reaction mixture was concentrated under vacuum
2. dissolutiondissolved in MeOH
3. filtrationfiltered through a 5 g SCX column
4. dissolutionanother small impurity so the product was dissolved in EtOAc (40 ml)
5. extractionextracted with HCl 2N (40 ml)
6. addition2 N NaOH was added to the aqueous layer until pH12 and product
7. extractionextracted with EtOAc (100 ml)
8. customThe organic phase was dried on a phase separation cartridge
9. concentrationconcentrated under vacuum
10. extractionso was extracted again with 2 N HCl (40 ml)
11. addition2 N NaOH was added to the aqueous layer until pH12 and product
12. extractionextracted with EtOAc (100 ml)
13. customThe organic layer was dried on a phase separation cartridge
14. concentrationconcentrated under vacuum
15. customto give the free base of the product
16. customthe solvent was evaporated

ORD-Eintrag

ord-1d969a86e9b844ca9ad021a4421df82b

Quelldatensatz

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08288388B2