Nitrogen → tert-Butyl 3-(3-methylpyridin-2-yl)benzoate

HRID 402554

Reaction equation

HRID 402554 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].N#N.[C:17]([O:21][C:22]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(Cl)Cl.CS(O)(=O)=O.[OH-].[Na+]>C1(C)C=CC=CC=1.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].O>[C:17]([O:21][C:22](=[O:23])[C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([C:2]2[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:29]=1)([CH3:20])([CH3:18])[CH3:19]

Participants

11

Reactant 7

HCID 947NitrogenHCID 6344DichloromethaneHCID 6395Methanesulfonic AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 2208322-Bromo-3-methylpyridineHCID 2773299(3-((Tert-butoxy)carbonyl)phenyl)boronic acid

Product 1

HCID 57516851tert-Butyl 3-(3-methylpyridin-2-yl)benzoateYield 82%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromo-3-methylpyridine (1.0 eq) was dissolved in toluene (12 vol). K2CO3 (4.8 eq) was added, followed by water (3.5 vol). The resulting mixture was heated to 65° C. under a stream of N2 for 1 hour. 3-(t-Butoxycarbonyl)phenylboronic acid (1.05 eq) and Pd(dppf)Cl2.CH2Cl2 (0.015 eq) were then added, and the mixture was heated to 80° C. After 2 hours, the heat was turned off, water was added (3.5 vol), and the layers were allowed to separate. The organic phase was then washed with water (3.5 vol) and extracted with 10% aqueous methanesulfonic acid (2 eq MsOH, 7.7 vol). The aqueous phase was made basic with 50% aqueous NaOH (2 eq) and extracted with EtOAc (8 vol). The organic layer was concentrated to afford crude tert-butyl-3-(3-methylpyridin-2-yl)benzoate (82%) that was used directly in the next step.

Workup

  1. customto separate
  2. washThe organic phase was then washed with water (3.5 vol)
  3. extractionextracted with EtOAc (8 vol)
  4. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-3c7c2f5ff82146528e888c36b85ef494
Source dataset
uspto-grants-2014_06
Patent number
US08742122B2

Linked notes

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