Sulfuric Acid → HCID 57433636, compound

HRID 1783822Notes

Reaction equation

HRID 1783822 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([CH:15]=2)[CH:13]=[CH:12][S:11]3)=[CH:4][C:3]=1[O:16][CH3:17].[C:18](OC(=O)C)(=[O:20])[CH3:19].S(=O)(=O)(O)O>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[C:18](=[O:20])[CH3:19])[CH:13]=[CH:12][S:11]3)=[CH:4][C:3]=1[O:16][CH3:17]

Participants

5

Reactant 3

HCID 1118Sulfuric Acid2×HCID 7918Acetic AnhydrideHCID 57433635HCID 57433635, compound

Product 1

HCID 57433636HCID 57433636, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of 6-(4-fluoro-3-methoxyphenyl)-imidazo[2,1-b]thiazole (1.0 g, 4.03 mmol) and acetic anhydride (25 ml), heated to 140° C., was added 43 μl of concentrated sulfuric acid. The reaction mixture was heated at 140° C. for 1 hour. The reaction was monitored by HPLC. After one hour, only 10% product was observed. Another 43 μl of concentrated sulfuric acid was added and the mixture was kept at 140° C. for 4 hours. The reaction mixture was then poured onto 50 ml of ice, and diluted with 50 ml of water and the resulting mixture was extracted two times with 100 ml each of ethyl acetate. The combined extracts were washed with two portions of 50 ml of water and two portions of 50 ml of saturated aqueous sodium chloride solution. The organic phase was dried with sodium sulfate, filtered and concentrated in vacuo, to give a brown solid. The product, -[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethanone, was purified by flash chromatography (gradient 25%-50% ethyl acetate in hexanes) and obtained as a pale yellow solid (1.12 g, 96%). 400 MHz 1H NMR (DMSO-d6) δ 8.44 (d, J=4.3 Hz, 1H), 7.56 (d, J=4.3 Hz, 1H), 7.43 (dd, J=8.2, 2.0 Hz, 1H), 7.34 (dd, J=11.7, 8.6 Hz, 1H), 7.21 (ddd, J=8.2, 4.3, 2.0 Hz, 1H), 3.89 (s, 3H), 2.14 (s, 3H). LCMS: 291 [M+H].

Workup

  1. temperatureThe reaction mixture was heated at 140° C. for 1 hour
  2. waitthe mixture was kept at 140° C. for 4 hours
  3. extractionthe resulting mixture was extracted two times with 100 ml each of ethyl acetate
  4. washThe combined extracts were washed with two portions of 50 ml of water and two portions of 50 ml of saturated aqueous sodium chloride solution
  5. dry with materialThe organic phase was dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a brown solid
  9. customThe product, -[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]ethanone, was purified by flash chromatography (gradient 25%-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-84734a6e0d0b4a9993a1fa8ca8aa0f7c
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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