p-Toluenesulfonic acid → HCID 86628116, Verbindung

Temperatur

-78 °C

To a solution of ethyl (1R,2R,3S,6S)-6-(aminomethyl)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)cyclohexanecarboxylate (0.07 g, 0.13 mmol, intermediate from Step E) in 30 mL dry toluene was added cyclopentane-1,3-dione (0.064 g, 0.65 mmol) and a catalytic amount (˜0.5 mg) of PTSA. The resulting mixture was heated at reflux for 1 hr. The solvent was removed under vacuum. The residue was dissolved in 10 mL toluene and was cooled to −78° C. under nitrogen. Dibal-H (2 mL, 1.0 M) was added. The reaction mixture was stirred for 16 hr at −78° C., quenched with water and diluted with ethyl acetate (10 mL). The organic layer was separated and the aqueous was extracted with ethyl acetate (10 mL). The combined extracts were washed with brine, dried over MgSO4, filtered and the solvent was removed under vacuum. The residue was purified by preparative TLC (silica gel eluting with 9:1 ethyl acetate: methanol) to give 8 mg of the title compound. MS: (MH)+ 574.2. The rest of the material was still unreacted ester.

1. temperatureThe resulting mixture was heated
2. temperatureat reflux for 1 hr
3. customThe solvent was removed under vacuum
4. dissolutionThe residue was dissolved in 10 mL toluene
5. additionDibal-H (2 mL, 1.0 M) was added
6. customquenched with water
7. additiondiluted with ethyl acetate (10 mL)
8. customThe organic layer was separated
9. extractionthe aqueous was extracted with ethyl acetate (10 mL)
10. washThe combined extracts were washed with brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. customthe solvent was removed under vacuum
14. customThe residue was purified by preparative TLC (silica gel eluting with 9:1 ethyl acetate: methanol)

ORD-Eintrag

ord-54fb843ef75b45fab0065de46c56dac2

Quelldatensatz

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07683068B2