Phosphorus oxychloride → HCID 86726359, compound

Participants

Reaction Steps

A solution of tert-butyl (2R,5R)-2-(2-(3-amino-5-fluoropyridin-4-yl)ethyl)-5-(2,2,2-trifluoroethylaminocarbonyloxymethyl)morpholine-4-carboxylate (Example 89, step 4) (64 mg, 0.13 mmol) and (2S,3S)-2-azido-3-(3,5-difluorophenyl)-3-(4-fluorophenyl)propanoic acid (43 mg, 0.13 mmol) in pyridine (0.5 mL) was cooled to −10° C. in an ice-acetone bath. To the stirred solution was added POCl3 (0.014 mL, 0.15 mmol) and the mixture was stirred for 30 min. The reaction was quenched by the addition of aqueous NaHCO3 solution and the resulting mixture was extracted with two portions of EtOAc. The combined EtOAc layers were dried (MgSO4), filtered, and the solvents were removed in vacuo. The residue was chromatographed on a 12 g SiO2 column using a gradient elution of 0-80% EtOAc in hexanes. Fractions containing product were combined and the solvents were removed in vacuo to give a gum. LC MS: RT=1.48 min, M+H=784 (2 min gradient)

Provenance & Evidence