4-Methylmorpholine → 1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3,3-dimethyl-L-prolinamide

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Reaction Steps

In an oven-dried 100 ml flask was dissolved 3,3-dimethyl-L-prolinamide (0.0174 mol, 2.46 g), (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (WO 2003101442, 0.0174 mol, 5.30 g), and 1-hydroxy-7-azabenzotriazole (0.0191 mol, 2.60 g) in 25 ml DMF with stirring under argon. To this solution was added N-methylmorpholine (0.0522 mol, 5.28 g) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.0191 mol, 3.67 g). The reaction was stirred at 20° C. for 16 hr after which time it was diluted with 300 ml water and extracted with ethylacetate (3×100 ml). The combined organics were washed with 100 ml 1M HCl followed by brine. The organics were dried over MgSO4, filtered and concentrated to a yellow oil and purified on 90 g silica (chloroform/methanol/water), yielding 4.72 g (63%) of 1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3,3-dimethyl-L-prolinamide as a white solid. LCMS (ESI+)=430 m/z (MH+). 1H NMR (400 MHz, CDCl3)— rotomers δ 8.20-7.86 (m, 1H), 7.49-7.30 (m, 5H), 6.01-5.50 (m, 2H), 5.05-4.70 (m, 2H), 3.89-3.56 (m, 4H), 3.14-2.90 (m, 2H), 2.16-2.05 (m, 1H), 1.89-1.40 (m, 10H), 1.13-1.06 (m, 6H), 1.02-0.84 (m, 2H).

Provenance & Evidence