Reaction #710594

Reaction equation

sodium triacetoxyborohydride

Triethylamine

5,7-dichloro-8-hydroxyquinoline-2-carboxaldehyde

5,7-Dichloro-8-hydroxyquinoline-2-carboxaldehyde

dimethylamine hydrochloride

→

5,7-dichloro-2-dimethylaminomethyl-quinolin-8-ol hydrochloride

Yield 73.0%

Solvents

Dichloromethane

1,2-dichloroethane

Conditions

Workup

1. 1
   Washthe mixture washed with saturated sodium bicarbonate (50 mL×3)
2. 2
   Dryingdried (Na2SO4)
3. 3
   Concentrationconcentrated
4. 4
   ExtractionThe resulting residue was extracted with diethyl ether (50 mL×4)
5. 5
   Concentrationconcentrated
6. 6
   workup.ADDITIONConcentrated hydrochloric acid (5 mL) was then added
7. 7
   Concentrationthe mixture concentrated in vacuo
8. 8
   WashThe residue, after washing with dichloromethane

Procedure

Triethylamine (0.55 mL) was added dropwise to a stirred solution of 5,7-dichloro-8-hydroxyquinoline-2-carboxaldehyde 17 (1.0 g, 4.13 mmol) and dimethylamine hydrochloride (365 mg, 4.48 mmol) in 1,2-dichloroethane (50 mL). After 5 minutes, sodium triacetoxyborohydride (1.2 g, 5.66 mmol) was added portionwise over 5 minutes. The mixture was then allowed to stir at RT overnight. Dichloromethane (100 mL) was added, the mixture washed with saturated sodium bicarbonate (50 mL×3), dried (Na2SO4), and concentrated. The resulting residue was extracted with diethyl ether (50 mL×4), the ethereal extracts combined and concentrated. Concentrated hydrochloric acid (5 mL) was then added and the mixture concentrated in vacuo. The process was repeated twice. The residue, after washing with dichloromethane, gave 5,7-dichloro-2-dimethylaminomethyl-quinolin-8-ol hydrochloride (PBT 1033) as a pale straw-coloured solid (0.96 g, 73%). 1H NMR (DMSO-d6, 400 MHz): δ 10.80 (s, 1H), 10.40 (br, 1H), 8.60 (d, J=8.6, 1H), 7.92 (s, 1H), 7.78 (d, J=8.6, 1H), 4.83 (d, J=5.3, 2 H), 2.94 (s, 3H), 2.92 (s, 3H).

Source