Water → HCID 66720992, compound

HRID 1040343Notes

Reaction equation

HRID 1040343 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=2OS(C(F)(F)F)(=O)=O)[CH:12]=[CH:13][C:14]=1[Cl:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>CN(C=O)C.CCOCC.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>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=2[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[CH3:34])[CH:12]=[CH:13][C:14]=1[Cl:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27332672-Methylphenyl boronic acidHCID 86637361HCID 86637361, compound

Product 1

HCID 66720992HCID 66720992, compoundYield 83.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
90 °C

Procedure

Stir a solution of 25 g (48.8 mmol) of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-{[(trifluoromethyl)sulphonyl]oxy}pyridine-2-carboxylate and 8.8 g (64.8 mmol) of 2-methylphenylboronic acid in 200 mL of anhydrous DMF for 15 min while bubbling with argon, then add 12.7 g (60 mmol) of anhydrous potassium phosphate (K3PO4) and 5.76 g (5 mmol) of Pd(PPh3)4 and stir the reaction mixture for 18 h at 90° C. under argon. Then distribute the reaction mixture at RT in 600 mL of ether/EtOAc 1:1 mixture and 600 ml of water. After extraction, extract the aqueous phase again with 100 mL of EtOAc, combine the organic phases and wash with 4×300 mL of water, dry over Na2SO4, then concentrate under reduced pressure. Purify the residue obtained by silica gel column chromatography, eluting with a heptane/EtOAc gradient from 0 to 20% of EtOAc. After concentration under reduced pressure, we obtain 18 g of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-(2-methylphenyl)pyridine-2-carboxylate in the form of oil.

Workup

  1. customwhile bubbling with argon
  2. customat RT
  3. extractionAfter extraction
  4. extractionextract the aqueous phase again with 100 mL of EtOAc
  5. washwash with 4×300 mL of water
  6. dry with materialdry over Na2SO4
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue
  9. customobtained by silica gel column chromatography
  10. washeluting with a heptane/EtOAc gradient from 0 to 20% of EtOAc
  11. concentrationAfter concentration under reduced pressure, we

Sources & evidence

ORD record
ord-4007db6a492543c59d815318dab2433f
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Reaction notes

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