Potassium Carbonate → tert-Butyl 3-(3-methylpyridin-2-yl)benzoate

HRID 2354938Notes

Reaction equation

HRID 2354938 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.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]>[CH3:8][C:7]1[C:2]([C:20]2[CH:21]=[C:16]([CH:17]=[CH:18][CH:19]=2)[C:14]([O:13][C:9]([CH3:11])([CH3:12])[CH3:10])=[O:15])=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2208322-Bromo-3-methylpyridineHCID 2773299(3-((Tert-butoxy)carbonyl)phenyl)boronic acid

Product 1

HCID 57516851tert-Butyl 3-(3-methylpyridin-2-yl)benzoateYield 63%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromo-3-methylpyridine (50.0 g, 291 mmol), 3-(tert-butoxycarbonyl)phenyl-boronic acid (68.4 g, 308 mmol), potassium carbonate (96.4 g, 697 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (Pd(dppf)Cl2, 3.19 g, 3.91 mmol) were dissolved in a mixture of 1.5 L of toluene and 350 mL of water. The resulting solution was stirred and heated at 80° C. for 16 hours. The reaction mixture was cooled to 25° C. and then the layers were separated. The organic layer was evaporated to dryness and was then purified on 3 kg of silica gel utilizing a gradient of 0-18.5% ethylacetate in hexanes to yield tert-butyl 3-(3-methylpyridin-2-yl)benzoate as a pale yellow oil (49.3 g, 63%). ESI-MS m/z calc. 269.1, found 270.2 (M+1)+. Retention time 0.93 minutes

Workup

  1. temperatureThe reaction mixture was cooled to 25° C.
  2. customthe layers were separated
  3. customThe organic layer was evaporated to dryness
  4. customwas then purified on 3 kg of silica gel utilizing a gradient of 0-18.5% ethylacetate in hexanes

Sources & evidence

ORD record
ord-2d485933801e4e01a4fd815100cbfc3f
Source dataset
uspto-grants-2010_07
Patent number
US07754739B2

Reaction notes

Loading…