Water → 5-(4-Chloro-phenyl)-6-cyclopropylmethoxy-2-trifluoromethyl-nicotinic acid ethyl ester

HRID 1159309Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[C:9](Br)[C:8]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)=[N:7][C:6]=1[C:17]([F:20])([F:19])[F:18])[CH3:2].[Cl:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:10]=[C:9]([C:26]2[CH:27]=[CH:28][C:23]([Cl:22])=[CH:24][CH:25]=2)[C:8]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)=[N:7][C:6]=1[C:17]([F:20])([F:19])[F:18])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

5-Bromo-6-cyclopropylmethoxy-2-trifluoromethyl-nicotinic acid ethyl ester (0.3 g, 0.81 mmol) was dissolved in dioxane (1.6 mL). To this solution was added with stirring [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) CH2Cl2 (33 mg, 0.04 mmol), 4-chlorophenylboronic acid (197 mg, 1.2 mmol) and sodium carbonate solution (2M, 1.2 mL). This mixture was heated to 80° C. for 5 h and cooled to room temperature. Water (150 mL) was added, the phases were separated and the water mixture was extracted with ethylacetate. Organic phases were pooled, dried with MgSO4 and the volatiles removed in vacuo. The residue was purified by flash chromatography on silica (dichloromethane/methanol, 4:1) to give the title compound (0.37 g) as light yellow oil; MS (ISP) 400.1 (M+H)+.

Workup

temperaturecooled to room temperature
customthe phases were separated
extractionthe water mixture was extracted with ethylacetate
dry with materialdried with MgSO4
customthe volatiles removed in vacuo
customThe residue was purified by flash chromatography on silica (dichloromethane/methanol, 4:1)

Sources & evidence

ORD record: ord-efdaa43b655a49588c8b7128fc8e7c7a
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07812028B2

Reaction notes

Loading…