Dimethylformamide → 3-(Methoxymethylcarbamoyl)pyrrolidine-1-carboxylic acid t-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Methanamine, N-methoxy-, hydrochloride (1:1)	HCID 81138	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1-((Tert-butoxy)carbonyl)pyrrolidine-3-carboxylic acid	HCID 2760529	—
Reactant	O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate	HCID 42624899	—
Solvent	Sodium Bicarbonate	HCID 516892	—
Product	3-(Methoxymethylcarbamoyl)pyrrolidine-1-carboxylic acid t-butyl ester	HCID 66673698	340.2%

Reaction Conditions

Temperature	0 °C

Reaction Steps

Pyrrolidine-1,3-dicarboxylic acid 1-t-butyl ester (0.7 g, 3.3 mmol), HCTU (2.0 g, 4.9 mmol), and HOBt (747 mg, 4.9 mmol), N,O-dimethylhydroxylamine HCl (1.6 g, 16.3 mmol) and DMF (10.0 mL, 129 mmol) were combined and cooled at 0° C. using an ice bath. DIPEA (5.7 mL, 32.5 mmol) was added slowly over 5 minutes. The mixture was allowed to warm to room temperature and stirred for 15 hours. The mixture was then diluted with sat. NaHCO3 (75 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with sat. NaCl (50 mL), dried over Na2SO4, filtered, concentrated under high vacuum to yield 2.9 g of the crude title compound as a mixture of the (R) and (S) enantiomers.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07888386B2
Source dataset	uspto-grants-2011_02
ORD ID	ord-fc5d0604fb1c445d8965daf4dfdb7ad4
Source note	uspto-grants-2011_02