Isopropylamine → di-tert-butyl (2R)-2-((1-methylethyl)carbamoyl)-1,4-piperazinedicarboxylate

https://huagongshe.com/reaction/1972607

Participants

Role	Name	HCID	Charge
Reactant	Isopropylamine	HCID 6363	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	(2R)-1,4-bis((tert-butoxy)carbonyl)piperazine-2-carboxylic acid	HCID 26339502	—
Solvent	Dimethylformamide	HCID 6228	—
Product	di-tert-butyl (2R)-2-((1-methylethyl)carbamoyl)-1,4-piperazinedicarboxylate	HCID 66583022	130.1%

Reaction Steps

A 20-mL vial was charged with ((2R)-1,4-bis(tert-butoxycarbonyl)-2-piperazinecarboxylic acid (1.57 g, 4.76 mmol, ASW MedChem Inc., New Brunswick, N.J.), HATU (2.17 g, 5.72 mmol, ChemImpex International Inc., Wood Dale, Ill.), propan-2-amine (0.450 mL, 5.28 mmol, Sigma-Aldrich, St. Louis, Mo.), DIPEA (1.70 mL, 9.76 mmol) and DMF (8 mL). The mixture was stirred at room temperature for 2.5 h. The reaction mixture was partitioned between water (80 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (50 mL). and the combined organic phases were washed with saturated aqueous NaHCO3 (100 mL), water (100 mL), then brine (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford di-tert-butyl (2R)-2-((1-methylethyl)carbamoyl)-1,4-piperazinedicarboxylate (2.30 g) as a light-brown foam.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08431563B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-0694084150db46259116c5722c84da70
Source note	uspto-grants-2013_04