4-(Bromoacetyl)benzonitrile → (R)-4-[2-(1-Methyl-2,2,2-trifluoroethylamino)-thiazol-4-yl]-benzonitrile

HRID 1191080Notes

Reaction equation

HRID 1191080 reaction equation
[C:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7](=O)[CH2:8]Br)=[CH:5][CH:4]=1)#[N:2].[CH3:13][C@@H:14]([NH:19][C:20]([NH2:22])=[S:21])[C:15]([F:18])([F:17])[F:16].C(=O)(O)[O-].[Na+]>C(O)C>[CH3:13][C@@H:14]([NH:19][C:20]1[S:21][CH:8]=[C:7]([C:6]2[CH:11]=[CH:12][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[N:22]=1)[C:15]([F:18])([F:17])[F:16]

Participants

5

Reactant 3

HCID 986544-(Bromoacetyl)benzonitrileHCID 516892Sodium BicarbonateHCID 58495653(R)-(1-Methyl-2,2,2-trifluoroethyl)-thiourea

Product 1

HCID 86624159(R)-4-[2-(1-Methyl-2,2,2-trifluoroethylamino)-thiazol-4-yl]-benzonitrileYield 52%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Dissolve 4-cyanophenacyl bromide (1.82 g, 8.14 mmol), (R)-(1-methyl-2,2,2-trifluoroethyl)-thiourea (1.4 g, 8.14 mmol) and sodium bicarbonate (0.68 g, 8.14 mmol) in absolute ethanol. Heat at reflux 2 h, cool to room temperature and let stand over 2 days. Filter and collect the resulting crude product as a tan solid. Purify by chromatography on silica gel (34 g) eluting with hexane/EtOAc (19:1 to 4:1 over 30 min, 4:1 over 10 min; 40 mL/min) to obtain the desired intermediate as a white solid (1.23 g, 52%). MS (ES+) m/z: 298 (M+H)+.

Workup

  1. temperatureHeat
  2. temperatureat reflux 2 h
  3. filtrationFilter
  4. customcollect the resulting crude product as a tan solid
  5. customPurify by chromatography on silica gel (34 g)
  6. washeluting with hexane/EtOAc (19:1 to 4:1 over 30 min, 4:1 over 10 min; 40 mL/min)

Sources & evidence

ORD record
ord-f3247a9d3cbc4635bbf3a28597dafcaf
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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