4-Methylmorpholine → Morpholine-4-carboxylic Acid

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).

1. customto obtain a homogenous solution
2. washwashed with saturated aqueous NaHCO3
3. dry with materialbrine, dried (MgSO4)
4. concentrationconcentrated
5. customThe product was purified from the residue by flash chromatography

ORD record

ord-f89aa9cac86948fda17eac28e120cb32

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492362B1