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

HRID 1159309
Notes
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Reaction equation

HRID 1159309 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 675049975-Bromo-6-cyclopropylmethoxy-2-trifluoromethyl-nicotinic acid ethyl ester

Product 1

HCID 675046855-(4-Chloro-phenyl)-6-cyclopropylmethoxy-2-trifluoromethyl-nicotinic acid ethyl esterYield 114.3%

Reagents, catalysts & solvents

2
HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

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

  1. temperaturecooled to room temperature
  2. customthe phases were separated
  3. extractionthe water mixture was extracted with ethylacetate
  4. dry with materialdried with MgSO4
  5. customthe volatiles removed in vacuo
  6. 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

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes