Hydrochloric Acid → 4-[(6-Benzyloxy-7-methoxy-3-nitroquinolin-4-yl)cyanomethyl]benzonitrile

HRID 2404228Notes

Reaction equation

HRID 2404228 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].[CH2:14]([O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH3:33])[N:28]=[CH:27][C:26]([N+:34]([O-:36])=[O:35])=[C:25]2Cl)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl>O1CCCC1.CN(C)C=O.O>[CH2:14]([O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH3:33])[N:28]=[CH:27][C:26]([N+:34]([O-:36])=[O:35])=[C:25]2[CH:9]([C:10]#[N:11])[C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 1366864-CyanophenylacetonitrileHCID 666119326-(Benzyloxy)-4-chloro-7-methoxy-3-nitroquinoline

Product 1

HCID 666325764-[(6-Benzyloxy-7-methoxy-3-nitroquinolin-4-yl)cyanomethyl]benzonitrileYield 92.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, 4-cyanophenylacetonitrile (3.86 g, 27.12 mmol) is dissolved in dry tetrahydrofuran (185 ml). Sodium hydride (60% dispersion in paraffin oil, 2.17 g, 54.25 mmol) is subsequently added in portions with ice-bath cooling, and the mixture is stirred for a further 30 min. A suspension of 6-benzyloxy-4-chloro-7-methoxy-3-nitro-quinoline (9.35 g, 27.12 mmol) in N,N-dimethylformamide (50 ml) is then added at room temperature, and the mixture is subsequently stirred for a further 2 h. When the reaction is complete, the mixture is added to 2.5 l of water and neutralised using 1.0 M hydrochloric acid with vigorous stirring. After stirring for 30 min, the suspension is acidified to about pH 2, and, after a further 30 min, the precipitate obtained is filtered off with suction, rinsed with water and dried overnight in a high vacuum. The crude product is subsequently purified over flash silica gel (solvent gradient cyclohexane/0-50% by vol. of ethyl acetate), giving 4-[(6-benzyloxy-7-methoxy-3-nitroquinolin-4-yl)cyanomethyl]benzonitrile (11.31 g, 25.11 mmol) as a solid having a melting point of 147.9° C. MS: 451.1 (M+H+), TLC (HPTLC) (HPTLC): Rf=0.68 (cyclohexane/ethyl acetate 1:1 parts by volume).

Workup

  1. temperaturecooling
  2. additionis then added at room temperature
  3. stirringthe mixture is subsequently stirred for a further 2 h
  4. stirringAfter stirring for 30 min
  5. waitafter a further 30 min
  6. customthe precipitate obtained
  7. filtrationis filtered off with suction
  8. washrinsed with water
  9. customdried overnight in a high vacuum
  10. customThe crude product is subsequently purified over flash silica gel (solvent gradient cyclohexane/0-50% by vol. of ethyl acetate)

Sources & evidence

ORD record
ord-b5d4643824b44acc8dc2643bbcc28471
Source dataset
uspto-grants-2014_08
Patent number
US08802712B2

Reaction notes

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