Ammonium Chloride → tert-butyl (5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oate

Participants

Role	Name	HCID	Charge
Reactant	Ammonium Chloride	HCID 25517	—
Reactant	(2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-methylbutanoic acid	HCID 978328	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	1-Hydroxybenzotriazole hydrate	HCID 2796029	—
Reactant	(3R,4S,5S)-tert-butyl 4-((S)-2-amino-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate	HCID 10546343	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	tert-butyl (5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oate	HCID 71294595	—

Reaction Steps

396 mg (1.1 mmol) N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methyl-L-valine was dissolved in DMF and then mixed in succession with 365 mg (1 mmol) tert-butyl-(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(L-valyl)amino]heptanoate (intermediate 2), 234 mg (1.2 mmol) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 187 mg (1.2 mmol) 1-hydroxy-1H-benzotriazole hydrate. The mixture was stirred over night at RT. The batch was then poured into a mixture of 50% saturated aqueous ammonium chloride solution and ethyl acetate. The organic phase was separated, washed in succession with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated. The residue was used directly in the next step without further purification.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09029406B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-e3712feaf9394067bcf214276a8e8206
Source note	uspto-grants-2015_05