Diisopropylethylamine → (2S,4R)-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid	HCID 88804	—
Reactant	Benzenamine, 4-(4-fluorophenoxy)-	HCID 147633	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(2S,4R)-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate	HCID 67010572	—

Reaction Steps

Step (a) A flask was charged with (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (2.1 g, 9.1 mmol), HATU (3.80 g, 10.0 mmol), 4-(4-fluorophenoxy)aniline (1.85 g, 9.09 mmol), DIEA (4.8 mL, 27 mmol) and DMF (20 mL). The reaction mixture was stirred at ambient temperature for 30 minutes and then quenched with saturated sodium bicarbonate (aq., 20 mL). The mixture was extracted with ethyl acetate (60 mL) and the extract was washed with deionized water (30 mL) and then brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give crude (2S,4R)-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate, which was carried forward without further purification.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08791102B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-c42665e3ff78450884cfa25e34ad041c
Source note	uspto-grants-2014_07