4-Methylmorpholine → Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMe

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	Diisopropylcarbodiimide	HCID 12734	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	(S)-2-((S)-2-((tert-Butoxycarbonyl)amino)-4-methylpentanamido)-4-methylpentanoic acid	HCID 7019882	—
Reactant	H-Lys(Z)-Leu-Leu-OMe.HCl	HCID 131721603	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Product	Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMe	HCID 12020547	86.4%

Reaction Conditions

Temperature	19 °C

Reaction Steps

4-Methylmorpholine (2.53 g, 25 mmol) was added to a solution of H-Lys(Z)-Leu-Leu-OMe·HCl (13.93 g, 25 mmol) in DMF (85.0 g) at 10° C. HOBt (3.38 g, 25 mmol), Boc-Leu-Leu-OH (8.61 g, 25 mmol) and DIC (3.47 g, 27.5 mmol) were added over 30 min at 8-10° C. An additional portion of DMF (5.0 g) was added and the reaction was kept at 8-10° C. for 16 h. The reaction was stirred at 18-20° C. for 3 h, cooled to 5-10° C. and treated with H2O (130.0 g). A solid precipitated at 25° C. which was filtered, washed with H2O and recrystallized from MeOH and H2O to give Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMe (SEQ. ID No. 2) (18.3 g, 86.4%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06013764
Source dataset	uspto-grants-2000_01
ORD ID	ord-53f7b4df04034305934cafec1fd80af7
Source note	uspto-grants-2000_01