Hydrochloric Acid → N-(2-(4-chlorophenyl)ethyl)-3-hydroxypyridine-2-Carboxamide

HRID 1797039Notes

Reaction equation

HRID 1797039 reaction equation
F[C:2](F)(F)[C:3]1[CH:16]=[CH:15][C:6](OC2C=CC(N)=CC=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](OC)[CH:21]=1.[ClH:39].C([N:42]([CH2:45]C)CC)C.[H][H]>CN(C1C=CN=CC=1)C.C(Cl)Cl.CCOC(C)=O.[Pd]>[Cl:39][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][CH2:45][NH:42][C:26]([C:24]2[C:23]([OH:29])=[CH:22][CH:21]=[CH:20][N:25]=2)=[O:27])=[CH:16][CH:15]=1

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 22175087N-(2-(4-chlorophenyl)ethyl)-3-hydroxypyridine-2-Carboxamide

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. Coupling Procedure C: Preparation of N-(4-Cyclohexylphenyl)-3-Hydroxypyridine-2-Carboxamide.

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-0e0c6a8b25d04dd9bf957e91b9893927
Source dataset
uspto-grants-2006_04
Patent number
US07034035B2

Reaction notes

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