Potassium Carbonate → Methyl 2'-[3-[(4-methoxybenzyl)oxy]-4-chlorophenyl]-3,5-dichloro-2,3'-bipyridine-6'-carboxylate

HRID 244060Notes

Reaction equation

HRID 244060 reaction equation
[CH3:1][O:2][C:3]1[CH:36]=[CH:35][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C:16]3[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=3B3OC(C)(C)C(C)(C)O3)[CH:12]=[CH:13][C:14]=2[Cl:15])=[CH:5][CH:4]=1.Br[C:38]1[C:43]([Cl:44])=[CH:42][C:41]([Cl:45])=[CH:40][N:39]=1.COCCOC.O.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:36]=[CH:35][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C:16]3[C:17]([C:38]4[C:43]([Cl:44])=[CH:42][C:41]([Cl:45])=[CH:40][N:39]=4)=[CH:18][CH:19]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[N:21]=3)[CH:12]=[CH:13][C:14]=2[Cl:15])=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 8170902-Bromo-3,5-dichloropyridineHCID 18180031Water 1,2-dimethoxyethaneHCID 66841210Methyl 6-[3-[(4-methoxybenzyl)oxy]-4-chlorophenyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate

Product 1

HCID 66841216Methyl 2'-[3-[(4-methoxybenzyl)oxy]-4-chlorophenyl]-3,5-dichloro-2,3'-bipyridine-6'-carboxylateYield 38.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 1 g (1.96 mmol) of methyl 6-[3-[(4-methoxybenzyl)oxy]-4-chlorophenyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate and 0.58 g (2.55 mmol) of 2-bromo-3,5-dichloropyridine in 10 mL of a 2/1 DME/water mixture, argon is sparged through for 10 minutes, followed by successive addition of 0.81 g (5.88 mmol) of K2CO3 and 0.159 g (0.14 mmol) of Pd(PPh3)4. The reaction mixture is heated for 4 hours at 80° C. and then cooled and diluted in 50 mL of EtOAc. The organic phase is washed with 2×20 mL of water, dried over Na2SO4 and then concentrated under reduced pressure. The residue is then purified on a column of silica gel, eluting with a cyclohexane/EtOAc gradient of from 0 to 40% EtOAc, to give 0.4 g of methyl 2′-[3-[(4-methoxybenzyl)oxy]-4-chlorophenyl]-3,5-dichloro-2,3′-bipyridine-6′-carboxylate in the form of an oil.

Workup

  1. customis sparged through for 10 minutes
  2. temperaturecooled
  3. washThe organic phase is washed with 2×20 mL of water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is then purified on a column of silica gel
  7. washeluting with a cyclohexane/EtOAc gradient of from 0 to 40% EtOAc

Sources & evidence

ORD record
ord-15aa13f6476e404f8ea33bd321b89329
Source dataset
uspto-grants-2014_02
Patent number
US08653276B2

Reaction notes

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