Hydrochloric Acid → (S)-3-phenyl-2-phenylamino-propionic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester

To a solution of 3-phenyl-2-(phenylamino)propanoic acid (I21) (1.21 g, 5.01 mmol) in dioxane, a 4M solution of HCl in dioxane (5 mL) is added and the reaction is allowed to stir at RT for 1 hour; the solvent is evaporated under reduced pressure to obtain a white solid which is dissolved in dry THF (70 mL). DCC (1.22 g, 6.01 mmol), HOBt (0.8 g, 6.0 mmol) and 3(R)-quinuclidinol (1.31 g, 10.1 mmol) are added to the resulting solution and the mixture stirred for 24 hours at RT under nitrogen flowstream (LC-MS monitoring: complete conversion). The solvent is evaporated. 1N HCl (20 mL) is added to the resulting crude and the aqueous layer is washed with EtOAc (2×50 mL); NaHCO3 is added to the aqueous layer (pH=7-8) and the product is extracted with DCM and dried over Na2SO4, to obtain 530 mg (35% yield) of diastereoisomer 1 of C22, which is further purified by preparative LC-MS to get the titled product as a brown oil (mixture of diastereoisomers that contains 20% of diastereoisomer 2 of C22, TFA salt).

1. customthe solvent is evaporated under reduced pressure
2. customto obtain a white solid which
3. stirringthe mixture stirred for 24 hours at RT under nitrogen flowstream (LC-MS monitoring: complete conversion)
4. customThe solvent is evaporated
5. addition1N HCl (20 mL) is added to the resulting crude
6. washthe aqueous layer is washed with EtOAc (2×50 mL)
7. additionNaHCO3 is added to the aqueous layer (pH=7-8)
8. extractionthe product is extracted with DCM
9. dry with materialdried over Na2SO4
10. customto obtain 530 mg (35% yield) of diastereoisomer 1 of C22, which
11. customis further purified by preparative LC-MS

ORD-Eintrag

ord-e84dc1e953274299b9d00d88c4ff9782

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08835682B2