Hydrochloric Acid → 3-hydroxy-4-methoxy-N-(4-(4-trifluoromethylphenoxy)phenyl)-pyridine-2-carboxamide

HRID 1059682Notes

Reaction equation

HRID 1059682 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][C:6]([O:7][C:8]2[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.Br[C:20]1[N:25]=[C:24]([C:26](Cl)=[O:27])[C:23]([O:29]CC2C=CC=CC=2)=[C:22]([O:37][CH3:38])[CH:21]=1.Cl.C(N(CC)CC)C.[H][H]>CN(C1C=CN=CC=1)C.C(Cl)Cl.CCOC(C)=O.[Pd]>[OH:29][C:23]1[C:24]([C:26]([NH:12][C:11]2[CH:10]=[CH:9][C:8]([O:7][C:6]3[CH:15]=[CH:16][C:3]([C:2]([F:17])([F:18])[F:1])=[CH:4][CH:5]=3)=[CH:14][CH:13]=2)=[O:27])=[N:25][CH:20]=[CH:21][C:22]=1[O:37][CH3:38]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27607514-(4-(Trifluoromethyl)phenoxy)anilineHCID 221750736-bromo-3-benzyloxy-4-methoxypyridine-2-carbonyl ChlorideHCID 178418361HCID 178418361, compound

Product 1

HCID 221751703-hydroxy-4-methoxy-N-(4-(4-trifluoromethylphenoxy)phenyl)-pyridine-2-carboxamideYield 43.3%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-(4-trifluoromethylphenoxy) aniline (0.20 g, 0.8 mmol) and DMAP (0.10 g, 0.085 mmol) in CH2Cl2 (10 mL) was added all at once a solution of 3-benzyloxy-6-bromo-4-methoxypyridin-2-carbonylchloride (3) (0.29 g, 0.8 mmol) in CH2Cl2 (5 mL). The resulting mixture was stirred overnight at room temperature then poured into 2N HCl (10 mL). The organic layer was separated and the aqueous layer extracted with CH2Cl2 (2×10 mL). The organic layers were combined, dried (MgSO4) and concentrated to give a gummy solid. This solid was taken up in EtOAc (20 mL), and triethylamine (0.80 g, 0.8 mmol) and 5% Pd on carbon (0.10 g) were added. The resulting mixture was subjected to a hydrogen atmosphere (initial pressure=50 psi) on a Parr shaker for 30 minutes. The mixture was filtered, washed with 0.1N HCl (20 mL), dried (MgSO4) and concentrated to give the title compound as an off-white solid (0.14 g), m.p.=122-129° C.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer extracted with CH2Cl2 (2×10 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto give a gummy solid
  6. customfor 30 minutes
  7. filtrationThe mixture was filtered
  8. washwashed with 0.1N HCl (20 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ee37703df6764cda94cb5a64db940311
Source dataset
uspto-grants-2003_02
Patent number
US06521622B1

Reaction notes

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