Hydrochloric Acid → 5-Quinolinecarboxylic acid, 7-fluoro-2-(4-fluorophenyl)-1,2,3,4-tetrahydro-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-, methyl ester

HRID 1617272Notes

Reaction equation

HRID 1617272 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:29]([O-])=O)[C:5]([C:12](=[O:28])/[C:13](/[C:22]2[N:26]([CH3:27])[N:25]=[CH:24][N:23]=2)=[CH:14]/[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].Cl>CO.[Fe]>[F:1][C:2]1[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:5]2[C:12](=[O:28])[CH:13]([C:22]3[N:26]([CH3:27])[N:25]=[CH:24][N:23]=3)[CH:14]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[NH:29][C:4]=2[CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 53353703(E)-Methyl 5-fluoro-2-(3-(4-fluorophenyl)-2-(1-methyl-1H-1,2,4-triazol-5-yl)acryloyl)-3-nitrobenzoate

Product 1

HCID 547529555-Quinolinecarboxylic acid, 7-fluoro-2-(4-fluorophenyl)-1,2,3,4-tetrahydro-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-, methyl esterYield 15.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 887MethanolSolvent

Procedure

To a solution of (E)-Methyl 5-fluoro-2-(3-(4-fluorophenyl)-2-(1-methyl-1H-1,2,4-triazol-5-yl)acryloyl)-3-nitrobenzoate (9) (214 mg, 0.5 mmol) in methanol (5 mL) was added concentrated HCl solution (w/w 37%, 1 mL), then reductive Fe powder (140 mg, 2.5 mmol) was added slowly to the reaction system. After the addition was complete the resulting mixture was refluxed for 24 hours. The reaction mixture was then filtered, concentrated, neutralized with saturated NaHCO3 (20 mL), and extracted with ethyl acetate (10 mL×3). The residue was purified by chromatography (ethyl acetate:petroleum ether=1:1) to give the title compound (5) (30 mg, yield 15%) as an off-white foam. LC-MS (ESI) m/z: 399 (M+H)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 3.56 (s, 3H), 3.86 (s, 3H), 7.02 (dd, 2H), 7.21 (dd, 2H), 7.90 (s, 1H), 8.08 (s, 1H), 8.26 (dd, 1H), 8.56 (dd, 1H).

Workup

  1. additionAfter the addition
  2. temperaturewas refluxed for 24 hours
  3. filtrationThe reaction mixture was then filtered
  4. concentrationconcentrated
  5. extractionextracted with ethyl acetate (10 mL×3)
  6. customThe residue was purified by chromatography (ethyl acetate:petroleum ether=1:1)

Sources & evidence

ORD record
ord-ab3c45cf9515406bb4ae7393dd24dcb2
Source dataset
uspto-grants-2014_07
Patent number
US08765945B2

Reaction notes

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