Triphenylphosphine → (1R)-N-(4-chloro-3-(1-(methylsulfonyl)pyrrolidin-3-yloxy)benzyl)-1-(3-chlorophenyl)ethanamine

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol 96 (150 mg, 506 μmol) in 5 mL of THF under N2 was added triphenylphosphine (146 mg, 557 μmol). The solution was chilled to 0° C. in an ice bath and then diisopropyl azodicarboxylate (108 μL, 557 μmol) was added dropwise to the reaction. After stirring for 15 min 0° C., a solution of 1-(methylsulfonyl)pyrrolidin-3-ol (84 mg, 506 μmol) in THF was added to the reaction. The reaction was allowed to warm to room temperature and it was stirred for 10 h. The reaction was concentrated and diluted with EtOAc. The organic solution was extracted with saturated NaHCO3, water, and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography using a 10% to 80% gradient of EtOAc in hexanes as the eluant. The desired fractions were combined and concentrated to give (1R)—N-(4-chloro-3-(1-(methylsulfonyl)pyrrolidin-3-yloxy)benzyl)-1-(3-chlorophenyl)ethanamine 99 (83 mg, 37% yield) as a colorless oil and as a mixture of diastereomers. 1H NMR (400 MHz, d4-methanol) δ ppm 1.26 (d, 1H) 1.73 (d, J=6.85 Hz, 3H) 2.25-2.32 (m, 2H) 2.91 (s, 3H) 3.51-3.60 (m, 2H) 3.62-3.66 (m, 2H) 4.00 (d, 1H) 4.20 (d, 1H) 4.50 (m, 1H) 5.08-5.13 (m, 1H) 6.99-7.07 (m, 1H) 7.14-7.18 (m, 1H) 7.43-7.52 (m, 4H) 7.57 (m, 1H). Mass spectrum: calculated for C20H24Cl2N2O3S 443.4. found 444.4 (M++1).

Provenance & Evidence