Reaction #2336529

Reaction equation

4-(4-trifluoromethylphenoxy) aniline

3-benzyloxy-6-bromo-4-methoxypyridin-2-carbonylchloride

6-BROMO-3-BENZYLOXY-4-METHOXYPYRIDINE-2-CARBONYL CHLORIDE

triethylamine

hydrogen

HCl

→

title compound

N-(2-(4-CHLOROPHENYL)ETHYL)-3-HYDROXYPYRIDINE-2-CARBOXAMIDE

Solvents

CH2Cl2

CH2Cl2

EtOAc

Conditions

Workup

1. 1
   OtherThe organic layer was separated
2. 2
   Extractionthe aqueous layer extracted with CH2Cl2 (2×10 mL)
3. 3
   Dryingdried (MgSO4)
4. 4
   Concentrationconcentrated
5. 5
   Otherto give a gummy solid
6. 6
   Otherfor 30 minutes
7. 7
   FiltrationThe mixture was filtered
8. 8
   Washwashed with 0.1N HCl (20 mL)
9. 9
   Dryingdried (MgSO4)
10. 10
    Concentrationconcentrated

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.

Source