4-Methylmorpholine → tert-butyl N-[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamate

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	N-Carbobenzoxy-L-valine	HCID 726987	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	4-Amino-2-(t-butyloxycarbonylamino)-1,5-diphenyl-3-hydroxypentane	HCID 14704377	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	tert-butyl N-[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamate	HCID 3011021	94.6%

Reaction Conditions

Temperature	0 °C

Reaction Steps

A solution of 39 mg (0.16 mmol) of Cbz-Val-OH, 52 mg (0.14 mmol) of the resultant compound of Example 11, and 23 mg (0.17 mmol) of 1-hydroxybenzotriazole in 2 ml of dimethylformamide was treated with 0.019 ml (0.17 mmol) of 4-methylmorpholine, cooled to 0° C., and treated with 33 mg (0.17 mmol) of N-ethyl-N'-(dimethylaminopropyl)-carbodiimide hydrochloride. After being stirred at ambient temperature overnight, the solution was diluted with ethyl acetate, washed sequentially with 10% citric acid, water, and aqueous NaHCO3, dried over Na2SO4, and concentrated in vacuo. Separation of the desired compounds by flash chromatography using methanol in chloroform gave 80 mg (95%) of the desired compound (Rf 0.40, 10% methanol in chloroform) as a white solid, m.p. 187°-187.5° C. Mass spectrum (M+H)+ =604.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US05142056
Source dataset	uspto-grants-1992_08
ORD ID	ord-347a4931554c49da9da29b0a95f1757a
Source note	uspto-grants-1992_08