Diisopropylethylamine → (1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate

https://huagongshe.com/reaction/1171950

Participants

Role	Name	HCID	Charge
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	N-Boc-5-(2-propen-1-yloxy)-L-norvaline	HCID 21080138	—
Reactant	(1R,2S)-ethyl 1-((3R,5S)-3-hydroxypyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride	HCID 67330424	—
Solvent	Water	HCID 962	—
Solvent	Toluene	HCID 1140	—
Solvent	Acetonitrile	HCID 6342	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate	HCID 70295348	—

Reaction Steps

(1R,2S)-ethyl-1-((2S,4R)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride salt (WO2005095403) (2.44 g, 7.76 mmol), (S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)-pentanoic acid (WO2004094452) (2.02 g, 7.39 mmol) and HATU (3.09 g, 8.13 mmol) in toluene (36 mL) and ACN (4 mL) was added DIEA (2.58 mL, 14.78 mmol) at 0° C. The reaction warmed to rt and stirred at rt for 1 hr. Ethyl acetate (30 mL) and water (20 mL) was added. The organic layer was separated and washed with brine, dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (Ethyl acetate) to give (1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate as white wax solid (3.55 g, 92%). MS: Calcd.: 523; Found: [M+H]+ 524.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07829665B2
Source dataset	uspto-grants-2010_11
ORD ID	ord-94e0e623d53c406f99a91d69fa890b26
Source note	uspto-grants-2010_11