Diisopropylethylamine → (2S,4S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 2733084	—
Reactant	(3-Chloro-2-fluorophenyl)methanamine	HCID 2773614	—
Reactant	(2S,4S)-1-(tert-butoxycarbonyl)-4-cyanopyrrolidine-2-carboxylic acid	HCID 14842641	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(2S,4S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 68283946	—

Reaction Steps

To a mixture of (2S,4S)-4-cyano-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (700 mg, 2.91 mmol), 3-chloro-2-fluorobenzylamine (558 mg, 3.50 mmol), HBTU (1.66 g, 4.37 mmol) in DMF (15 mL) was added DIPEA (1.5 mL, 8.74 mmol) and the resolution mixture was stirred at RT under nitrogen for 48 h. The mixture was poured in water and extracted with EtOAc (2×). The combined organic extracts were washed with water (1×), dried (Na2SO4), filtered and concentrated. The crude material was purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1) to give the desired compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.40; MS: 404.0 [M+Na]+, 380.0 [M−H]−, tR (HPLC conditions a): 3.45 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09085555B2
Source dataset	uspto-grants-2015_07
ORD ID	ord-e6601b86aa814b728a231b9ab0e44bd8
Source note	uspto-grants-2015_07