Diisopropylethylamine → [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-carbamic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(2R)-2-(((tert-butoxy)carbonyl)amino)pentanoic acid	HCID 6995000	—
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	3-fluoroazetidine Hydrochloride	HCID 10125054	—
Solvent	Dimethylformamide	HCID 6228	—
Product	[(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-carbamic acid tert-butyl ester	HCID 71279341	110.1%

Reaction Steps

A round-bottomed flask was charged with Boc-D-norvaline (300 mg, 1.38 mmol) and 3-fluoroazetidine hydrochloride (216 mg, 1.93 mmol). DMF (6 ml) was added followed by N,N-diisopropylethylamine (0.65 ml, 3.72 mmol) and HATU (578 mg, 1.52 mmol). The yellow reaction mixture was stirred at room temperature for 48 h the quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated to give 417 mg of [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-carbamic acid tert-butyl ester as a light yellow solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08658646B2
Source dataset	uspto-grants-2014_02
ORD ID	ord-ea59b331e47d426182d8ae6c6a724198
Source note	uspto-grants-2014_02