Sodium Sulfite → 3-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

HRID 1893420Notes

Reaction equation

HRID 1893420 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][N:17]2[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=[C:16]2[CH2:15]1)=[O:13].[Br:27]N1C(=O)CCC1=O.S([O-])([O-])=O.[Na+].[Na+]>CN(C)C=O>[Br:27][C:20]1[N:17]2[CH2:18][CH2:19][N:14]([C:12]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:10])([F:9])[F:11])[C:2]=3[Cl:1])=[O:13])[CH2:15][C:16]2=[N:22][C:21]=1[C:23]([F:26])([F:24])[F:25]

Participants

5

Reactant 3

HCID 24437Sodium SulfiteHCID 67184N-bromobutanimideHCID 497850117-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

Product 1

HCID 497852033-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazineYield 62.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.181 g, 0.455 mmol, Example 2) was dissolved in N,N-dimethylformamide (DMF) (2 mL) and treated with N-bromosuccinimide (NBS, 0.097 g, 0.546 mmol). The solution was stirred at room temperature for 16 hr. The mixture was poured onto water (100 ml) containing 1% sodium sulfite (w/w) and extracted into ethyl acetate (3×50 ml). The combined extracts were washed with brine (50 ml), dried over anhydrous sodium sulfate and concentrated to afford crude product (0.323 g). The crude product was purified by mass-directed automated preparative HPLC to afford 3-bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.135 g, 0.283 mmol, 62.2% yield).

Workup

  1. additionThe mixture was poured onto water (100 ml)
  2. extractionextracted into ethyl acetate (3×50 ml)
  3. washThe combined extracts were washed with brine (50 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto afford crude product (0.323 g)
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-ccd8be96665040e5a4897c296dc645f8
Source dataset
uspto-grants-2013_08
Patent number
US08513248B2

Reaction notes

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