Water → HCID 68182943, compound

HRID 1615547Notes

Reaction equation

HRID 1615547 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14]3[CH:15]=[CH:16][S:17][C:13]=3[C:12](=[N:18]O)[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[OH2:20]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:10][CH2:11][NH:18][C:12](=[O:20])[C:13]3[S:17][CH:16]=[CH:15][C:14]2=3)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 962WaterHCID 86669800HCID 86669800, compound

Product 1

HCID 68182943HCID 68182943, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

In a 250-ml round bottomed flask equipped with a stirbar was placed 4-(3,4-dichlorophenyl)-N-hydroxy-5,6-dihydro-1-benzothiophen-7(4H)-imine (1.25 g, 4.00 mmol) and polyphosphoric acid (40 g, 200 mmol). The resulting mixture was heated at 130° C. under an atmosphere of nitrogen with stirring for ˜4 hours, leaving a dark brown mixture. The mixture was allowed to cool to rt then water and ethyl acetate were added. The mixture was stirred briefly then transferred to a separatory funnel. The organic layer was separated then the aqueous layer was extracted with additional ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and evaporated to leave crude product as a brown oil. The residue was purified using column chromatography on silica gel (120 g RediSep column, gradient 0% ethyl acetate in dichloromethane to 90% ethyl acetate in dichloromethane over 20 minutes) give the product 1.08 g (86% yield) product as a light tan solid. LCMS: (FA) ES+ 312, 314. 1H NMR (400 MHz, DMSO) δ 8.24-8.12 (s, 1H), 7.65-7.59 (d, J=5.2 Hz, 1H), 7.60-7.51 (d, J=8.3 Hz, 1H), 7.45-7.36 (d, J=2.1 Hz, 1H), 7.11-7.01 (dd, J=8.3, 2.1 Hz, 1H), 6.64-6.51 (d, J=5.2 Hz, 1H), 4.56-4.42 (dd, J=8.8, 5.5 Hz, 1H), 3.25-3.03 (m, 2H), 2.34-2.18 (m, 1H), 2.10-1.95 (m, 1H).

Workup

  1. customIn a 250-ml round bottomed flask equipped with a stirbar
  2. customleaving a dark brown mixture
  3. temperatureto cool to rt
  4. stirringThe mixture was stirred briefly
  5. customthen transferred to a separatory funnel
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with additional ethyl acetate
  8. washwashed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customto leave crude product as a brown oil
  13. customThe residue was purified
  14. customon silica gel (120 g RediSep column, gradient 0% ethyl acetate in dichloromethane to 90% ethyl acetate in dichloromethane over 20 minutes)

Sources & evidence

ORD record
ord-05f013ff8a6f4a149190cdca07c47abf
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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