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

HRID 82339

Reaction equation

HRID 82339 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) is dissolved in toluene (12 vol). K2CO3 (4.8 eq) is added followed by water (3.5 vol) and the mixture 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) are then added and the mixture is heated to 80° C. After 2 hours, the heat is turned off, water is added (3.5 vol) and the layers are allowed to separate. The organic phase is then washed with water (3.5 vol) and extracted with 10% aqueous methanesulfonic acid (2 eq MsOH, 7.7 vol). The aqueous phase is made basic with 50% aqueous NaOH (2 eq) and extracted with EtOAc (8 vol). The organic layer is concentrated to afford crude tert-butyl-3-(3-methylpyridin-2-yl)benzoate (82%) that is used directly in the next step.

Workup

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

Sources & evidence

ORD record
ord-84731088f4f743a9ac8c2caf4f96cd92
Source dataset
uspto-grants-2014_09
Patent number
US08846718B2

Linked notes

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