Potassium Phosphate, Tribasic → HCID 24891582, compound

HRID 1908289Notes

Reaction equation

HRID 1908289 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH2:4][NH:5][C:6]([C:8]1[C:13]([OH:14])=[CH:12][C:11](OS(C(F)(F)F)(=O)=O)=[CH:10][N:9]=1)=[O:7].[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=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:23])[CH2:4][NH:5][C:6]([C:8]1[C:13]([OH:14])=[CH:12][C:11]([C:29]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:24])[CH:30]=2)=[CH:10][N:9]=1)=[O:7]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734323(3-Chlorophenyl)boronic acidHCID 59030680HCID 59030680, compound

Product 1

HCID 24891582HCID 24891582, compoundYield 53%

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 [(3-hydroxy-5-trifluoromethane-sulfonyloxy-pyridine-2-carbonyl)-amino]-acetic acid methyl ester, 5, (0.30 g, 0.84 mmol) in 1,4-dioxane (10 mL) at room temperature under N2 is added 3-chlorophenylboronic acid (0.196 g, 1.26 mmol), Pd(dppf)Cl2 (0.068 g, 0.0084 mmol) and K3PO4 (0.195 g, 0.92 mmol). The resulting suspension is heated in a sealed tube at 85° C. for 16 hours. After this time, the mixture is cooled to room temperature and concentrated under reduced pressure. The residue is then treated with 1M HCl (1 mL) and diluted with EtOAc. The organic layer is separated, washed with H2O, saturated aqueous NaCl and concentrated under reduced pressure. The crude material is purified over silica (EtOAc:heptane 3:7). The resulting solid can be crystallized from EtOAc/heptane to afford 0.143 g (53% yield) of the desired compound as a colorless solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.77 (1H, s), 8.36 (1H, t, J=5.7 Hz), 8.24 (1H, d, J=1.8 Hz), 7.50-7.53 (1H, m), 7.39-7.42 (2H, m), 7.34-7.37 (2H, m), 4.20 (2H, d, J=5.9 Hz), 3.76 (3H, s). HPLC-MS: m/z.

Workup

  1. temperatureAfter this time, the mixture is cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue is then treated with 1M HCl (1 mL)
  4. additiondiluted with EtOAc
  5. customThe organic layer is separated
  6. washwashed with H2O, saturated aqueous NaCl
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material is purified over silica (EtOAc:heptane 3:7)
  9. customThe resulting solid can be crystallized from EtOAc/heptane

Sources & evidence

ORD record
ord-ad89a807f2b84f80b34c026ab9a17139
Source dataset
uspto-grants-2013_12
Patent number
US08598210B2

Reaction notes

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