4-Methylmorpholine → 2-(4-(1H-pyrazol-1-yl)phenyl)-N,2-dimethoxy-N-methylacetamide

HRID 56498Notes

Reaction equation

C[C:2]([C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:18]=[CH:17][CH:16]=[N:15]2)=[CH:10][CH:9]=1)([O:6][CH3:7])[C:3]([OH:5])=O.CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:35][NH:36][O:37][CH3:38]>ClCCl.C([O-])(O)=O.[Na+]>[N:14]1([C:11]2[CH:10]=[CH:9][C:8]([CH:2]([O:6][CH3:7])[C:3]([N:36]([O:37][CH3:38])[CH3:35])=[O:5])=[CH:13][CH:12]=2)[CH:18]=[CH:17][CH:16]=[N:15]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 2-(4-(1H-pyrazol-1-yl)phenyl)-2-methoxyacetic acid (0.18 g, 0.77 mmol) in dry dichloromethane (5 mL) under argon was added N-methylmorpholine (0.18 mL, 1.7 mmol). The reaction mixture was cooled to 0° C., isobutylchloroformate was added, (0.11 mL, 0.85 mmol) and the mixture was stirred for 40 minutes. N,O-dimethylhydroxylamine hydrochloride (0.098 g, 1 mmol) was then added in one portion and slowly allowed to warm to room temperature and stirred for 18 hours. The mixture was diluted with saturated aqueous NaHCO3 and extracted with EtOAc. The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification by chromatography (0-80% EtOAc-hexanes) provided 2-(4-(1H-pyrazol-1-yl)phenyl)-N,2-dimethoxy-N-methylacetamide (0.16 g, 76% yield).

Workup

temperatureto warm to room temperature
stirringstirred for 18 hours
extractionextracted with EtOAc
washThe combined organics were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customPurification by chromatography (0-80% EtOAc-hexanes)

Sources & evidence

ORD record: ord-270dd1c6e4a848f3a88a3b0c86518f21
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434707B2

Reaction notes

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