Hydrochloric Acid → 4-[(2-Ethylquinolin-4-yloxy)methyl]phenylboronic acid hydrochloride

HRID 5672

Reaction equation

HRID 5672 reaction equation
[CH2:1]([C:3]1[CH2:12][C:11](=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)[CH3:2].NC1C=CC=CC=1.C(CC(OCC)=O)(=O)CC.[H-].[Na+].Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([B:41]2[O:46]CC(C)(C)C[O:42]2)=[CH:37][CH:36]=1.CC1C=CC(B(O)O)=CC=1.CC(C)(CO)CO.BrN1C(=O)CCC1=O.[ClH:74]>CN1C(=O)CCC1.C1CCCCC1.C(OCC)(=O)C.N(C(C)(C)C#N)=NC(C)(C)C#N.O>[ClH:74].[CH2:1]([C:3]1[CH:12]=[C:11]([O:13][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([B:41]([OH:46])[OH:42])=[CH:37][CH:36]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)[CH3:2]

Participants

15

Reactant 9

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 24758Sodium hydrideHCID 31344Neopentyl glycolHCID 67184N-bromobutanimideHCID 78656Ethyl 3-oxovalerateHCID 79799Tolylboronic acidHCID 110005212-(4-(Bromomethyl)phenyl)-5,5-dimethyl-1,3,2-dioxaborinaneHCID 150208512-ethyl-3H-quinolin-4-one

Product 1

HCID 677828274-[(2-Ethylquinolin-4-yloxy)methyl]phenylboronic acid hydrochloride

Reagents, catalysts & solvents 5

HCID 6547AzobisisobutyronitrileCatalystHCID 962WaterSolvent2×HCID 8078CyclohexaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

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).

Workup

  1. temperatureby heating
  2. temperatureheating the mixture
  3. temperatureat reflux for 3 hours
  4. customremoving
  5. filtrationby filtration]
  6. additionwas added
  7. temperaturethe mixture was heated at 60°-70° C. for 18 hours
  8. temperatureto cool
  9. additionacetic acid was then added until the mixture
  10. customthe organic phase was separated
  11. washwashed with water
  12. dry with materialdried (MgSO4)
  13. customVolatile material was removed by evaporation
  14. customto give a crystalline solid
  15. stirringthe mixture was stirred for 18 hours
  16. filtrationThe resultant precipitate was collected by filtration
  17. washwashed with ethyl acetate
  18. customdried

Sources & evidence

ORD record
ord-ff3a359235274b109e5176e13886b94a
Source dataset
uspto-grants-1993_09
Patent number
US05245035

Linked notes

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