Dimethylformamide → (R)-N-[1-[(hydroxyamino)carbonyl]-2-methylpropyl]-1-(4-methylphenyl)cyclopropanecarboxamide

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
Reactant	Ethyl Acetate	HCID 8857	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1-(p-Tolyl)cyclopropanecarboxylic acid	HCID 98639	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Product	(R)-N-[1-[(hydroxyamino)carbonyl]-2-methylpropyl]-1-(4-methylphenyl)cyclopropanecarboxamide	HCID 9882466	52%

Reaction Conditions

Temperature	70 °C

Reaction Steps

N,N-diisopropylethylamine (0.539 mL, 4 eq) was added to a mixture of the crude amine hydrochloride (200 mg) from reaction (1b), 1-(4-methylphenyl)-1-cyclopropane carboxylic acid (163 mg, 1.2 eq) and HATU (441 mg, 1.5 eq) in N,N-dimethylformamide (1 mL). The mixture was stirred at room temperature overnight and at 70° C. for 90 min. Following addition of ethyl acetate (100 mL), the mixture was washed with 1:1 mixture of 1 N hydrochloric acid-saturated brine (2×10 mL), dried (MgSO4) and concentrated. Silica gel column chromatography (ethyl acetate-hexane, 40:60) yielded the desired product (127 mg, 52% for two steps). MS found: (M+H)+=381.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06376665B1
Source dataset	uspto-grants-2002_04
ORD ID	ord-120696545c394922ba8455a52aa0effd
Source note	uspto-grants-2002_04