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

HRID 1891337Notes

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

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

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

Sources & evidence

ORD record: ord-ae3c1cffc1ab4d53806301f8868a08e6
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507534B2

Reaction notes

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