Cesium carbonate → 2-Hydroxy-5-phenylnicotinic acid

HRID 2117142Notes

Reaction equation

HRID 2117142 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.Cl[Pd]Cl>[O:11]=[C:5]1[C:6]([C:7]([OH:9])=[O:8])=[CH:10][C:2]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:3][NH:4]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 178418525HCID 178418525, compound

Product 1

HCID 103759752-Hydroxy-5-phenylnicotinic acidYield 18.1%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-bromo-2-hydroxynicotinic acid (436 mg, 2.00 mmol, Syn. Comm., 19 (3&4), 553-559 (1989)), phenylboronic acid (248 mg, 2.03 mmol), Cs2CO3 (1.20 g) and PdCl2 [(t-Bu) 2P(OH)] 2 (170 mg, CombiPhos Catalysts, Inc. Princeton, N.J.) in DMF (10 mL) and water (1.0 mL) was purged with Ar gas and heated at 110° C. for 6 h. Additional phenylboronic acid (75 mg) was added and the mixture was heated at 110° C. for 5 h. To the reaction was added TFA (3 mL), and the mixture was concentrated in vacuo to a volume of ˜12 mL. The mixture was purified by preparative HPLC to afford the desired product (78 mg, 18%). 1H NMR (DMF-d7) δ 14.8 (br s, 1H), 13.8 (br s, 1H), 8.73 (s, 1H), 8.46 (s, 1H), 7.74 (d, 1H, J=7.2 Hz), 7.53-7.42 (m, 3H), 5.81 (s, 1H).

Workup

  1. customwater (1.0 mL) was purged with Ar gas
  2. additionAdditional phenylboronic acid (75 mg) was added
  3. temperaturethe mixture was heated at 110° C. for 5 h
  4. additionTo the reaction was added TFA (3 mL)
  5. concentrationthe mixture was concentrated in vacuo to a volume of ˜12 mL
  6. customThe mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-5d4643b337ed49aa95cf4af81f40e6d1
Source dataset
uspto-grants-2008_10
Patent number
US07439246B2

Reaction notes

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