4-Methylmorpholine → Morpholine-4-carboxylic Acid

Participants

Reaction Steps

A solution of (R)-3-[2-(1,1-difluoro-methoxy)-phenylmethanesulfonyl]-2-[(1-morpholin-4-ylmethanoyl)amino]propionic acid (200 mg, 0.473 mmol), provided as in Reference 1, in CH2Cl2 (3 mL) was combined with HATU (270 mg, 0.71 mmol), HOAt (64.3 mg, 0.473 mmol), 4-amino-1-methyl-piperidine-4-carbonitrile (98 mg, 0.71 mmol), N-methylmorpholine (0.156 mL, 1.42 mmol) and them DMF (3 mL) to obtain a homogenous solution. The mixture was stirred at room temperature for 16 hours, diluted with ethyl acetate (150 mL), washed with saturated aqueous NaHCO3 and then brine, dried (MgSO4) and concentrated. The product was purified from the residue by flash chromatography to provide morpholine-4-carboxylic acid {(R)-1-(4-cyano-1-methyl-piperidin4-ylcarbamoyl)-2-[2-(1,1-difluoro-methoxy-phenylmethanesulfonyl]-ethyl}-amide. 1H NMR: (DMSO) 8.62 (s, 1H), 7.51-7.23 (m, 4H), 7.13 (t, JH,F=74 Hz, 1H), 7.06 (d, J=8.6 Hz, 1H), 4.70 (m, 1H), 4.57 (s, 2H), 3.57-3.25 (m, 10 H), 2.62-1.82 (m, 1H).

Provenance & Evidence