4-Fluorobenzaldehyde → (E)-Methyl 5-fluoro-2-(3-(4-fluorophenyl)-2-(1-methyl-1H-1,2,4-triazol-5-yl)acryloyl)-3-nitrobenzoate

HRID 1617269Notes

Reaction equation

HRID 1617269 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([N+:22]([O-:24])=[O:23])[C:6]([C:13](=[O:21])[CH2:14][C:15]2[N:19]=[CH:18][N:17](C)[N:16]=2)=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=1.N1CCC[C@H:35]1C(O)=O>CS(C)=O>[F:2][C:3]1[CH:4]=[C:5]([N+:22]([O-:24])=[O:23])[C:6]([C:13](=[O:21])/[C:14](/[C:15]2[N:16]([CH3:35])[N:17]=[CH:18][N:19]=2)=[CH:30]/[C:29]2[CH:32]=[CH:33][C:26]([F:25])=[CH:27][CH:28]=2)=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9]

Participants

5

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 145742L-ProlineHCID 67355822methyl 5-fluoro-2-(2-(1-methyl-1H-1,2,4-triazole-3-yl)acetyl)-3-nitrobenzoate hydrochloride

Product 1

HCID 53353703(E)-Methyl 5-fluoro-2-(3-(4-fluorophenyl)-2-(1-methyl-1H-1,2,4-triazol-5-yl)acryloyl)-3-nitrobenzoateYield 40%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of methyl 5-fluoro-2-(2-(1-methyl-1H-1,2,4-triazol-5-yl)acetyl)-3-nitrobenzoate (4) (580 mg, 2 mmol) and 4-fluorobenzaldehyde (488 mg, 4 mmol) in dimethylsulfoxide (2 mL) was added L-proline (230 mg, 2 mmol). The resulting mixture was kept with stirring at 45° C. for 48 hours. The reaction system was then partitioned between ethyl acetate (50 mL) and water (30 mL), and the organic phase was washed with water (20 mL×3), dried with Na2SO4, concentrated in vacuo, and purified by column chromatography (ethyl acetate:petroleum ether=1:3) to give the title compound (9) as a pale yellow foam (340 mg, yield 40%). LC-MS (ESI) m/z: 429 (M+1)+. 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. customThe reaction system was then partitioned between ethyl acetate (50 mL) and water (30 mL)
  2. washthe organic phase was washed with water (20 mL×3)
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated in vacuo
  5. custompurified by column chromatography (ethyl acetate:petroleum ether=1:3)

Sources & evidence

ORD record
ord-d861f510f49c4635b038774cb543a588
Source dataset
uspto-grants-2014_07
Patent number
US08765945B2

Reaction notes

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