Acetic Acid → (R)-1-{5-[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamino]-2-methyl-benzyl}-pyrrolidine-3-carboxylic acid

To a solution of aldehyde INT 33 (2.50 g, 7.32 mmol) and (R)-pyrrolidine-3-carboxylic acid (0.93 g, 8.05 mmol) in MeOH (74 mL) was added HOAc (0.42 mL, 7.32 mmol) followed by PS—CNBH3 (2.5 mmol/g, 2.93 g, 7.32 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was filtered through Celite. The filtrate was concentrated. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3 and water. The aqueous layers were extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (CH2Cl2/MeOH) to afford the title compound Example 21.

1. filtrationThe mixture was filtered through Celite
2. concentrationThe filtrate was concentrated
3. washwashed with saturated aqueous NaHCO3 and water
4. extractionThe aqueous layers were extracted with EtOAc (2×)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by chromatography on silica gel (CH2Cl2/MeOH)

ORD record

ord-85fc6a5fcf504090b9a28880a614e43d

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791100B2