Reaction #5768

Reaction equation

2-ethyl-4-quinolone

hydrochloric acid

aniline

ethyl propionylacetate

sodium hydride

N-bromosuccinimide

2-(4-bromomethylphenyl)-5,5-dimethyl-1,3,2-dioxaborinane

4-methylphenylboronic acid

2,2-dimethylpropan-1,3-diol

→

4-[(2-ethylquinolin-4-yloxy)methyl]phenylboronic acid hydrochloride

Solvents

water

NMP

ethyl acetate

water

NMP

cyclohexane

cyclohexane

Conditions

Workup

1. 1
   Temperatureby heating
2. 2
   Temperatureheating the mixture
3. 3
   Temperatureat reflux for 3 hours
4. 4
   Otherremoving
5. 5
   Filtrationby filtration]
6. 6
   workup.ADDITIONwas added
7. 7
   Temperaturethe mixture was heated at 60°-70° C. for 18 hours
8. 8
   Temperatureto cool
9. 9
   workup.ADDITIONacetic acid was then added until the mixture
10. 10
    Otherthe organic phase was separated
11. 11
    Washwashed with water
12. 12
    Dryingdried (MgSO4)
13. 13
    OtherVolatile material was removed by evaporation
14. 14
    Otherto give a crystalline solid
15. 15
    workup.STIRRINGthe mixture was stirred for 18 hours
16. 16
    FiltrationThe resultant precipitate was collected by filtration
17. 17
    Washwashed with ethyl acetate
18. 18
    Otherdried

Procedure

A solution of 2-ethyl-4-quinolone (6.9 g; 0.04 mole), (prepared using a similar procedure to that described in Org. Syn., Coll., Vol. III, p. 374 and p. 593 from aniline and ethyl propionylacetate) in (NMP) (50 ml) was added over 30 minutes to a stirred suspension of sodium hydride (1.6 g of a 60% dispersion in mineral oil; 0.04 mole) in NMP (50 ml) and the mixture stirred for 30 minutes. A solution of 2-(4-bromomethylphenyl)-5,5-dimethyl-1,3,2-dioxaborinane in cyclohexane [previously prepared by heating a mixture of 4-methylphenylboronic acid (6.8 g) and 2,2-dimethylpropan-1,3-diol (5.2 g) in cyclohexane (150 ml) at reflux with azeotropic removal of water, followed by the addition of N-bromosuccinimide (8.9 g) and azo(bisisobutyronitrile) (0.2 g), heating the mixture at reflux for 3 hours, and removing suspended succinimide by filtration] was added and the mixture was heated at 60°-70° C. for 18 hours. The mixture was allowed to cool and acetic acid was then added until the mixture was at pH 4, followed by water (200 ml) and ethyl acetate (200 ml). The mixture was stirred for 20 minutes and then the organic phase was separated, washed with water and dried (MgSO4). Volatile material was removed by evaporation to give a crystalline solid. The solid was dissolved in ethyl acetate (150 ml), concentrated hydrochloric acid (3 ml) and water (3 ml) were added and the mixture was stirred for 18 hours. The resultant precipitate was collected by filtration, washed with ethyl acetate and dried to give 4-[(2-ethylquinolin-4-yloxy)methyl]phenylboronic acid hydrochloride (7 g) as a solid; NMR (d4 -methanol): 1.5(t,3H), 3.21(q,2H), 5.78(s,2H), 7.55(s,1H), 7.6-8.15(m,7H), 8.40(d,2H).

Source