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

HRID 843388

Reaction equation

HRID 843388 reaction equation
[CH:1](N(CC)C(C)C)([CH3:3])[CH3:2].[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2([C:20]([OH:22])=O)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1.CN(C([O:30][N:31]1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O:50][CH2:51][CH3:52])(=O)C.C[N:54](C)C=O>>[OH:30][NH:31][C:51]([C@H:52]([NH:54][C:20]([C:17]1([C:14]2[CH:13]=[CH:12][C:11]([CH3:10])=[CH:16][CH:15]=2)[CH2:18][CH2:19]1)=[O:22])[CH:1]([CH3:3])[CH3:2])=[O:50]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 986391-(p-Tolyl)cyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 9882466(R)-N-[1-[(hydroxyamino)carbonyl]-2-methylpropyl]-1-(4-methylphenyl)cyclopropanecarboxamideYield 52%

Conditions

Temperature
70 °C

Procedure

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.

Workup

  1. washthe mixture was washed with 1:1 mixture of 1 N hydrochloric acid-saturated brine (2×10 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-120696545c394922ba8455a52aa0effd
Source dataset
uspto-grants-2002_04
Patent number
US06376665B1

Linked notes

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