3,5-Bis(trifluoromethyl)benzyl bromide → HCID 58966545, compound

HRID 390749Notes

Reaction equation

HRID 390749 reaction equation
[Br:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=2[CH:20]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:21]([CH3:23])[CH3:22])=[N:6][CH:7]=1.CC(C)([O-])C.[K+].[F:36][C:37]([F:51])([F:50])[C:38]1[CH:39]=[C:40]([CH:43]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:45]=1)[CH2:41]Br>C1COCC1>[F:36][C:37]([F:50])([F:51])[C:38]1[CH:39]=[C:40]([CH:43]=[C:44]([C:46]([F:49])([F:47])[F:48])[CH:45]=1)[CH2:41][N:8]([C:5]1[CH:4]=[N:3][C:2]([Br:1])=[CH:7][N:6]=1)[CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:13]=[CH:12][C:11]=1[CH:20]([N:24]1[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1)[CH:21]([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 23665647Potassium tert-butoxideHCID 86614959HCID 86614959, compound

Product 1

HCID 58966545HCID 58966545, compoundYield 80.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a flask charged with (5-Bromo-pyrazin-2-yl)-[2-(2-methyl-1-morpholin-4-yl-propyl)-5-trifluoromethyl-benzyl]-amine (94 mg, 0.198 mmol) was added THF (2 mL) followed by potassium t-butoxide (28 mg, 0.249 mmol). After 4 minutes, 3,5-bis(trifluoromethyl)benzyl bromide (0.05 mL; 0.272 mol) was added. The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water and diluted with ethyl acetate. The mixture was washed with 2N HCl. The aqueous layer was basified with 1N NaOH and extracted with ethyl acetate (2×). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (silica gel) (eluting with 10-40% ethyl acetate in hexanes) to afford the title compound (111 mg, 0.159 mmol).

Workup

  1. customThe reaction mixture was quenched with water
  2. additiondiluted with ethyl acetate
  3. washThe mixture was washed with 2N HCl
  4. extractionextracted with ethyl acetate (2×)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (silica gel) (eluting with 10-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-26d54f958b204ceaa29b70b27c3c7740
Source dataset
uspto-grants-2013_02
Patent number
US08383660B2

Reaction notes

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