Hydrochloric Acid → N-[3-Acetyl-5-(pentafluorosulfanyl)phenyl]acetamide

HRID 532414Notes

Reaction equation

HRID 532414 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:14]=[C:15]([S:17]([F:22])([F:21])([F:20])([F:19])[F:18])[CH:16]=1)[C:8](N(OC)C)=[O:9])(=[O:3])[CH3:2].[CH3:23][Si](C)(C)[N-][Si](C)(C)C.[Li+].C[Mg]Br.Cl>C1COCC1.C(OCC)(=O)C.O>[C:8]([C:7]1[CH:6]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:16]=[C:15]([S:17]([F:22])([F:18])([F:20])([F:21])[F:19])[CH:14]=1)(=[O:9])[CH3:23]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 581368203-Acetylamino-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamideHCID 178418573HCID 178418573, compound2×

Product 1

HCID 58136897N-[3-Acetyl-5-(pentafluorosulfanyl)phenyl]acetamideYield 82.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Acetylamino-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamide (1.2 g) was dissolved in absolute THF (30 ml) and stirred at 0° C. with lithium hexamethyldisilazide (721 μl; density: 0.8 g/1; 23% in tert-butyl methyl ether) for 30 min. At 0° C., methylmagnesium bromide (2.87 ml, 3 M in diethyl ether) was then added dropwise while stirring. After stirring at RT for 2.5 h, further methylmagnesium bromide (1 ml, 3 M in diethyl ether) was added and the mixture was stirred again for 2.5 h. For workup, 1 N hydrochloric acid was added dropwise while cooling with ice, followed by water and ethyl acetate. The organic phase was removed and the water phase was extracted twice more with ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, filtered and concentrated. The crude product (1.03 g) was combined with a crude product prepared in the same way (75 mg) and purified using silica gel with dichloromethane-methanol as the eluent. 860 mg of the desired compound were obtained. LC-MS rt: 1.34 min [M+H]+: 304.0

Workup

  1. stirringAfter stirring at RT for 2.5 h
  2. stirringthe mixture was stirred again for 2.5 h
  3. temperaturewhile cooling with ice
  4. customThe organic phase was removed
  5. extractionthe water phase was extracted twice more with ethyl acetate
  6. dry with materialThe combined ethyl acetate phases were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customprepared in the same way (75 mg)
  10. custompurified

Sources & evidence

ORD record
ord-9c5e3cd1332a46799334b99572871282
Source dataset
uspto-grants-2014_10
Patent number
US08853206B2

Reaction notes

Loading…