4-Methylmorpholine → HCID 18391822, compound

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-	HCID 117439	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	1-Hydroxybenzotriazole hydrate	HCID 2796029	—
Reactant	Methylamine hydrochloride	HCID 6364545	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Product	HCID 18391822	HCID 18391822	84%

Reaction Conditions

Temperature	10 °C

Reaction Steps

To a solution of N-(tert-butoxycarbonyl)-L-tyrosine (300 g, 1.07 mol) in DMF (2 L) were successively added methylamine hydrochloride (86.4 g, 1.28 mol), 1-hydroxybenzotriazole monohydrate (163 g, 1.07 mol, hereinafter to be abbreviated as HOBt.H2O), N-methylmorpholine (258 mL, 2.35 mol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (245 g, 1.28 mol, hereinafter to be abbreviated as WSCI.HCl), under ice-cooling (internal temperature 10° C.). The reaction mixture was stirred for 70 hr while gradually raising the temperature to room temperature. The reaction mixture was poured into iced water (10 L), and the precipitate was collected by filtration and washed with water and ether. The obtained precipitate was recrystallized from ethyl acetate (7 L) to give the title compound (265 g, 84%) as white crystals.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06989401B2
Source dataset	uspto-grants-2006_01
ORD ID	ord-7f57d569a0934a8fbdaef6c65a97f38a
Source note	uspto-grants-2006_01