Diisopropylethylamine → [(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acid	HCID 7005057	—
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	Azetidine-3-carbonitrile hydrochloride	HCID 45072465	—
Solvent	Dimethylformamide	HCID 6228	—
Product	[(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester	HCID 71279421	119.3%

Reaction Steps

A round-bottomed flask was charged with Boc-D-tert-leucine (300 mg, 1.3 mmol) and azetidine-3-carbonitrile hydrochloride (231 mg, 1.95 mmol). DMF (6 ml) was added followed by N,N-diisopropylethylamine (0.68 ml, 3.9 mmol) and HATU (543 mg, 1.43 mmol). The light yellow solution was stirred at room temperature for 48 h then 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 afford 458 mg of [(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester as a light yellow oil.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08658646B2
Source dataset	uspto-grants-2014_02
ORD ID	ord-5a14c4fe870146f090c27e393277ed11
Source note	uspto-grants-2014_02