Sulfuric Acid → HCID 118079994, compound

HRID 1485667Notes

Reaction equation

HRID 1485667 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[C@@H:7]([CH3:18])[CH2:6][N:5]2S(C1C=CC(C)=CC=1)(=O)=O.ClCCl.S(=O)(=O)(O)O>O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:17])[C:13]([F:15])([F:14])[F:16])[C@@H:7]([CH3:18])[CH2:6][NH:5]2

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 6344DichloromethaneHCID 118080067HCID 118080067, compound

Product 1

HCID 118079994HCID 118079994, compoundYield 99.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A 3-L, three-necked, round bottomed flask fitted with a nitrogen inlet, magnetic stir bar, and thermocouple was charged with (S)-1-(6-bromo-2-methyl-4-tosyl-3,4-dihydroquinoxaline-1(2H)-yl)-2,2,2-trifluoroethanone (106.81 g, 224 mmol), dichloromethane (1070 mL), and sulfuric acid (18 M, 119 mL, 2238 mmol). The reaction mixture stirred at rt for 1 h and was then cooled to 0° C. Water (1070 mL) was slowly added in 100 mL portions, while maintaining the internal temperature at ca. 0° C. (Note: the internal temperature rose from ca. 2.6° C. to 23.8° C. with each addition). After the final water addition, the internal temperature was 34° C., and the mixture was cooled to rt. The aqueous layer was separated extracted with dichloromethane (700 mL). The combined organic layers were washed with water (700 mL) and then concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 100% dichloromethane). The product-containing fractions were combined and concentrated under reduced pressure. Further drying under vacuum (ca. 17 Torr) at rt afforded (S)-1-(6-bromo-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)-2,2,2-trifluoroethanone (71.8 g, 99%) as a brown solid. MS (ESI, pos. ion) m/z 323[M+1]+.

Workup

  1. temperaturewas then cooled to 0° C
  2. temperaturewhile maintaining the internal temperature at ca. 0° C. (Note
  3. additionthe internal temperature rose from ca. 2.6° C. to 23.8° C. with each addition)
  4. customwas 34° C.
  5. temperaturethe mixture was cooled to rt
  6. customThe aqueous layer was separated
  7. extractionextracted with dichloromethane (700 mL)
  8. washThe combined organic layers were washed with water (700 mL)
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by column chromatography on silica gel (eluting with 100% dichloromethane)
  11. concentrationconcentrated under reduced pressure
  12. customFurther drying under vacuum (ca. 17 Torr) at rt

Sources & evidence

ORD record
ord-c929e182437a4385a8ab00aec5b6174a
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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