Hydrochloric Acid → HCID 68687136, compound

HRID 1159119Notes

Reaction equation

HRID 1159119 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][N:11]2[C:12](=[O:23])[C:13]3[C:18]([CH:10]2[CH:9]1[CH3:26])=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.S(=O)(=O)(O)O.[Br:33]N1C(=O)CCC1=O>>[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][N:11]2[C:12](=[O:23])[C:13]3[C:18]([CH:10]2[CH:9]1[CH3:26])=[CH:17][C:16]([Br:33])=[CH:15][C:14]=3[C:19]([F:20])([F:22])[F:21])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 67184N-bromobutanimideHCID 16115384HCID 16115384, compound

Product 1

HCID 68687136HCID 68687136, compoundYield 59.3%

Procedure

To N-(t-butoxycarbonyl)-(±)-1,3,4,10b-tetrahydro-1-methyl-7-trifluoromethyl-pyrazino[2,1-a]isoindol-6(2H)-one (364 mg, 0.98 mmol) was added concentrated aqueous hydrogen chloride (5 mL). The resulting mixture was stirred for five minutes and then concentrated. The resulting residue was treated with concentrated aqueous sulfuric acid (2.0 mL) and N-bromosuccinimide (193 mg, 1.1 mmol). The resulting brown solution was degassed (vacuum then argon), covered with aluminum foil and stirred in the dark for 24 h. The reaction was then diluted with ice water and basified with saturated aqueous sodium bicarbonate. The resulting mixture was diluted with ethyl acetate (15 mL) and treated with di-tert-butyl dicarbonate (excess). After 1 hr, the reaction washed with ethyl acetate (3×50 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by flash column chromatography (SiO2, 0-30% ethyl acetate in hexanes) to afford N-(t-butoxycarbonyl)-(±)-1,3,4,10b-tetrahydro-9-bromo-1-methyl-7-trifluoromethyl-pyrazino[2,1-a]isoindol-6(2H)-one (261 mg, 59%) as a white foam-like solid. MS (ESI) 449, 451 (M+H).

Workup

  1. concentrationconcentrated
  2. customThe resulting brown solution was degassed (vacuum
  3. stirringstirred in the dark for 24 h
  4. additionThe reaction was then diluted with ice water
  5. additionThe resulting mixture was diluted with ethyl acetate (15 mL)
  6. additiontreated with di-tert-butyl dicarbonate (excess)
  7. waitAfter 1 hr
  8. washthe reaction washed with ethyl acetate (3×50 mL)
  9. dry with materialthe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting residue was purified by flash column chromatography (SiO2, 0-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-717a538f548842a9b3869aa6fb685e3e
Source dataset
uspto-grants-2010_10
Patent number
US07812024B2

Reaction notes

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