Diisopropylethylamine → di-tert-butyl (2R)-2-(((3S)-3-methyl-4-morpholinyl)carbonyl)-1,4-piperazinedicarboxylate

Participants

Reaction Steps

A 100-mL round-bottomed flask was charged with (R)-1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (2.04 g, 6.17 mmol, ASW MedChem. Inc., New Brunswick, N.J.), (S)-3-methylmorpholine (0.657 g, 6.50 mmol, Synthetech Inc., Albany, Oreg.), HATU (2.83 g, 7.45 mmol, ChemImpex International Inc., Wood Dale, Ill.), DIPEA (2.20 mL, 12.6 mmol) and DMF (12 mL). The reaction mixture was stirred at room temperature for 1 h. After this time, additional HATU (0.475 g) was added and the stirring at room temperature was resumed for 2 days. The reaction mixture was partitioned between water (120 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×40 mL). The combined organic phases were washed with water (50 mL), saturated aqueous NaHCO3 (50 mL), water (50 mL) and saturated aqueous NaCl (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford di-tert-butyl (2R)-2-(((3S)-3-methyl-4-morpholinyl)carbonyl)-1,4-piperazinedicarboxylate (2.71 g) as a light-brown solid.

Provenance & Evidence