Triethylamine → 3-Chloro-2-cyclopropylamino-4,5-difluorobenzoic acid

HRID 10302Notes

Reaction equation

Br[C:2]1[C:10]([Cl:11])=[C:9]([F:12])[C:8]([F:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH:14]1([NH2:17])[CH2:16][CH2:15]1.C([O-])(=O)C.[K+].C(N(CC)CC)C>C(O)(C)C>[Cl:11][C:10]1[C:2]([NH:17][CH:14]2[CH2:16][CH2:15]2)=[C:3]([CH:7]=[C:8]([F:13])[C:9]=1[F:12])[C:4]([OH:6])=[O:5]

Participants

Conditions

Temperature: 80 °C

Procedure

In a sealed tube a mixture of 2-bromo-3-chloro-4,5-difluorobenzoic acid (Example 20, 7.96 g, 29.3 mmol), cyclopropyl amine (4.20 mL, 58.7 mmol), potassium acetate (5.77 g, 58.6 mmol), cupric acetate monohydrate (0.50 g, 2.5 mmol), and triethylamine (4.9 mL, 35.19 mmol) in isopropyl alcohol is stirred at 80° C. After 16 hours, the reaction mixture is concentrated under vacuum, and the resulting residue is dissolved in ethyl acetate. The organic layer is washed with 1.0 M hydrochloric acid, water, and brine. The organic layer is dried over MgSO4 and filtered. The filtrate is concentrated under vacuum and purified via flash column chromatography (5% isopropyl alcohol/1% formic acid/94% dichloromethane) to afford the title compound (4.62 g). MS CI: m/z 248 (MH+).

Workup

concentrationthe reaction mixture is concentrated under vacuum
dissolutionthe resulting residue is dissolved in ethyl acetate
washThe organic layer is washed with 1.0 M hydrochloric acid, water, and brine
dry with materialThe organic layer is dried over MgSO4
filtrationfiltered
concentrationThe filtrate is concentrated under vacuum
custompurified via flash column chromatography (5% isopropyl alcohol/1% formic acid/94% dichloromethane)

Sources & evidence

ORD record: ord-ab04c13734c14f0eb76b4fd42879a70a
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07094780B1

Reaction notes

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