Diisopropylethylamine → (S)-4-benzyl 1-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1,4-dicarboxylate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Benzenamine, 4-(4-fluorophenoxy)-	HCID 147633	—
Reactant	1-(1,1-Dimethylethyl) 4-(phenylmethyl) (2S)-1,2,4-piperazinetricarboxylate	HCID 7010652	—
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	(S)-4-benzyl 1-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1,4-dicarboxylate	HCID 56954160	100.4%

Reaction Steps

Step (a) A flask was charged with (S)-4-(benzyloxycarbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1 g, 2.74 mmol), obtained commercially, 4-(4-fluorophenoxy)aniline (558 mg, 2.75 mmol), DIEA (3 mL, 17.3 mmol), HATU (1.15 g, 3.03 mmol) and DMF (8 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give (S)-4-benzyl 1-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1,4-dicarboxylate (1.46 g, 2.75 mmol), 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-6584f05368124300a644410ab6ffd0ec
Source note	uspto-grants-2014_07