Dimethylformamide dimethyl acetal → HCID 54025290, compound

HRID 258162Notes

Reaction equation

HRID 258162 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:3]=1[CH2:4][S:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][C:13]([O:15][CH3:16])=[O:14].CO[CH:24](OC)[N:25]([CH3:27])[CH3:26].S(C1C=CC(C)=CC=1)([O-])(=O)=O.[NH+]1C=CC=CC=1>CO>[CH3:24][N:25]([CH3:27])[CH:26]=[C:12]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[S:5][CH2:4][C:3]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:2]=1[F:1])[C:13]([O:15][CH3:16])=[O:14]

Participants

5

Reactant 3

HCID 78373Dimethylformamide dimethyl acetalHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 53706799HCID 53706799, compound

Product 1

HCID 54025290HCID 54025290, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl [2-(2,5-difluorobenzylthio)phenyl]acetate, (15.6 g), dimethylformamide dimethylacetal (23 ml) and pyridinium tosylate (0.2 g) was heated on an oil bath at 140° with distillation of methanol for 4 hours. Excess dimethylformamide dimethylacetal was evaporated under reduced pressure and the residue purified by silica gel column chromatography to give an oil which was recrystallised from diisopropyl ether to give methyl 3-dimethylamino-2-[2-(2,5-difluorobenzylthio)phenyl]prop-2-enoate, mp 97.5°-99° (compound 1A). A mixture of this product (7.26 g), dissolved in acetone (500 ml) and water (15 ml), and Amberlyst 15 (an acidic ion-exchange resin) was stirred at room temperature for 24 hours. The mixture was filtered and the filtrate evaporated, extracted with ether and the extract worked up to give methyl 3-hydroxy-2-[2-(2,5-difluorobenzylthio) phenyl]prop-2-enoate, as a yellow oil, (compound 1B). This (5.3 g) was dissolved in tetrahydrofuran (70 ml) and sodium hydride (0.495 g of 80% dispersion in oil) was added and the mixture stirred for 30 minutes at room temperature. Methyl iodide (2.34 g) was added and the mixture stirred at room temperature overnight and then heated under reflux for 4 hours. Solvent was evaporated and the resulting oil was partitioned between ethyl acetate/ether and water and the organic phase dried and evaporated. The resulting oil was applied to a silica gel chromatography column and eluted with hexane/ethyl acetate to give crude methyl 3-methoxy-2-[2-(2,5-difluorobenzylthio) phenyl]prop-2-enoate, one fraction as the Z-isomer and another fraction as E-isomer. The Z-isomer (2.6 g) was dissolved in toluene (70 ml) and two drops of concentrated sulphuric acid added. The mixture was heated under reflux for two hours, whereby the Z-isomer was converted to the E-isomer. The mixture was washed with water, dried and evaporated and the resulting oil combined with the previously obtained E-isomer. The combined fractions were further purified by column chromatography to give pure methyl (E)-3-methoxy-2-[2-(2,5-difluorobenzylthio) phenyl]prop-2-enoate, as a light brown oil. (Compound 1C).

Workup

  1. customExcess dimethylformamide dimethylacetal was evaporated under reduced pressure
  2. customthe residue purified by silica gel column chromatography
  3. customto give an oil which
  4. customwas recrystallised from diisopropyl ether

Sources & evidence

ORD record
ord-df6d0f36e76f482a888d360f35e51e38
Source dataset
uspto-grants-1993_11
Patent number
US05264609

Reaction notes

Loading…