Dichloromethane → 5-Phenoxynicotinic acid methyl ester

HRID 1845022Notes

Reaction equation

HRID 1845022 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[N:6][CH:5]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(Cl)Cl.CCN(CC)CC>CCOC(C)=O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([O:10][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]=[N:6][CH:5]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 66827Phenylboronic AcidHCID 354317Methyl 5-hydroxypyridine-3-carboxylate

Product 1

HCID 592551745-Phenoxynicotinic acid methyl ester

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

0.31 g (2 mmol) of 5-hydroxy-nicotinic acid methyl ester, 0.73 g (4 mmol) of copper acetate, ˜1 g of 4 Å molecular sieves and 0.85 g (7 mmol) of phenylboronic acid were combined in a flask charged with 20 mL of DCM and 2.0 mL (14 mmol) of Et3N. This reaction slurry was stirred overnight at r.t. The reaction mixture was then diluted with 200 mL of EtOAc and washed 3 times with 10% K2CO3. The organic layer was then dried with Na2SO4, evaporated and purified by flash column chromatography (EtOAc/hexanes=1:2) to give 5-phenoxy-nicotinic acid methyl ester, which was subsequently hydrolyzed according to general procedure B to give 5-phenoxy-nicotinic acid and used in the next step without further purification.

Workup

  1. washwashed 3 times with 10% K2CO3
  2. dry with materialThe organic layer was then dried with Na2SO4
  3. customevaporated
  4. custompurified by flash column chromatography (EtOAc/hexanes=1:2)

Sources & evidence

ORD record
ord-4380b06c626f400aafeda93faefed902
Source dataset
uspto-grants-2015_02
Patent number
US08946259B2

Reaction notes

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