Potassium Phosphate, Tribasic → 2-{[5-(3-Chlorophenyl)-3-hydroxy-pyridine-2-carbonyl]-amino}-2-methyl-propionic acid methyl ester

HRID 1024519Notes

Reaction equation

HRID 1024519 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C:4]([NH:7][C:8]([C:10]1[C:15]([OH:16])=[CH:14][C:13](OS(C(F)(F)F)(=O)=O)=[CH:12][N:11]=1)=[O:9])([CH3:6])[CH3:5].[Cl:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[CH3:1][O:2][C:3](=[O:25])[C:4]([NH:7][C:8]([C:10]1[C:15]([OH:16])=[CH:14][C:13]([C:31]2[CH:30]=[CH:29][CH:28]=[C:27]([Cl:26])[CH:32]=2)=[CH:12][N:11]=1)=[O:9])([CH3:6])[CH3:5]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734323(3-Chlorophenyl)boronic acidHCID 595130782-[(3-Hydroxy-5-trifluoromethanesulfonyloxy-pyridine-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester

Product 1

HCID 248911462-{[5-(3-Chlorophenyl)-3-hydroxy-pyridine-2-carbonyl]-amino}-2-methyl-propionic acid methyl esterYield 73%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a degassed solution of 2-[(3-hydroxy-5-trifluoromethanesulfonyloxy-pyridine-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester (0.17 g, 0.44 mmol) in 1,4-dioxane (3 mL) at room temperature under N2 is added 3-chlorophenyl boronic acid (0.082 g, 0.53 mmol), K3PO4 (0.112 g, 0.53 mmol) and Pd(dppf)Cl2 (0.036 g, 0.04 mmol). The resulting suspension is heated to 85° C. in a sealed tube for 20 hours. After cooling, the reaction solution is filtered through Celite™ and the collected solids are washed with additional MeOH. The filtrate and washings are concentrated under reduced pressure and the residue dissolved in CH2Cl2 and washed with 10% citric acid. The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product is purified over silica (EtOAc:heptane 1:4) to afford 0.112 g (73% yield) of the desired compound as a colorless oil. 1H NMR (250 MHz, CDCl3) δ ppm 11.83 (1H, br s), 8.29 (1H, br s), 8.10 (1H, d, J=2.0 Hz), 7.40 (1H, m), 7.08-7.34 (4H, m), 3.65 (3H, s), 1.55 (6H, s). HPLC-MS: m/z 349 [M+H]+.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction solution is filtered through Celite™
  3. washthe collected solids are washed with additional MeOH
  4. concentrationThe filtrate and washings are concentrated under reduced pressure
  5. dissolutionthe residue dissolved in CH2Cl2
  6. washwashed with 10% citric acid
  7. dry with materialThe organic layer is dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product is purified over silica (EtOAc:heptane 1:4)

Sources & evidence

ORD record
ord-5375de37144b4564a95692556119172b
Source dataset
uspto-grants-2014_05
Patent number
US08722895B2

Reaction notes

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