Potassium Phosphate, Tribasic → HCID 66840971, compound

HRID 244070Notes

Reaction equation

HRID 244070 reaction equation
[CH3:1][O:2][C:3]1[CH:35]=[CH:34][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C:16]3[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=3OS(C(F)(F)F)(=O)=O)[CH:12]=[CH:13][C:14]=2[Cl:15])=[CH:5][CH:4]=1.[CH3:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CCOCC.CCOC(C)=O.O>CN(C=O)C.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>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C:16]3[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=3[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=3[CH3:36])[CH:12]=[CH:13][C:14]=2[Cl:15])=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27332672-Methylphenyl boronic acidHCID 86649787HCID 86649787, compoundHCID 86649789HCID 86649789, compound

Product 1

HCID 66840971HCID 66840971, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2.6 g (4.88 mmol) of methyl 6-[3-[(4-methoxybenzyl)oxy]-4-chlorophenyl]-5-{[(trifluoromethyl)sulfonyl]oxy}pyridine-2-carboxylate (Example 1.4) and 880 mg (6.48 mmol) of 2-methylphenylboronic acid in 20 mL of anhydrous DMF is stirred for 15 minutes while sparging with argon, followed by addition of 1.27 g (6 mmol) of anhydrous K3PO4 and 0.58 g (0.5 mmol) of Pd(PPh3)4, and the reaction mixture is stirred for 18 hours at 90° C. under argon. The reaction medium is then poured at room temperature into 120 ml of a 1/1/2 ether/EtOAc/water mixture. After extracting, the aqueous phase is re-extracted with 10 mL of EtOAc, the organic phases are combined and washed with 4×30 mL of water, dried over Na2SO4 and then concentrated under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, eluting with a heptane/EtOAc gradient of from 0 to 20% EtOAc. After concentrating under reduced pressure, 1.8 g of methyl 6-[3-[(4-methoxybenzyl)]oxy-4-chlorophenyl]-5-(2-methylphenyl)pyridine-2-carboxylate are obtained in the form of an oil.

Workup

  1. customwhile sparging with argon
  2. extractionAfter extracting
  3. extractionthe aqueous phase is re-extracted with 10 mL of EtOAc
  4. washwashed with 4×30 mL of water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. customis purified by chromatography on a column of silica gel
  9. washeluting with a heptane/EtOAc gradient of from 0 to 20% EtOAc
  10. concentrationAfter concentrating under reduced pressure, 1.8 g of methyl 6-[3-[(4-methoxybenzyl)]oxy-4-chlorophenyl]-5-(2-methylphenyl)pyridine-2-carboxylate
  11. customare obtained in the form of an oil

Sources & evidence

ORD record
ord-9ceeacfe65db493b9c0e18c314c77dfa
Source dataset
uspto-grants-2014_02
Patent number
US08653276B2

Reaction notes

Loading…