Triethylamine → N-{4-[3-(4-Chloro-phenyl)-3,8-diaza-bicyclo[3.2.1]oct-8-yl]-butyl}-2,2,2-trifluoro-acetamide

HRID 1266985Notes

Reaction equation

HRID 1266985 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:15][CH:14]3[NH:16][CH:11]([CH2:12][CH2:13]3)[CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[F:24][C:25]([F:39])([F:38])[C:26]([NH:28][CH2:29][CH2:30][CH2:31][CH2:32]OS(C)(=O)=O)=[O:27]>O1CCCC1.C(=O)(O)[O-].[Na+]>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH:11]3[N:16]([CH2:32][CH2:31][CH2:30][CH2:29][NH:28][C:26](=[O:27])[C:25]([F:24])([F:38])[F:39])[CH:14]([CH2:13][CH2:12]3)[CH2:15]2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 185451893-(4-Chlorophenyl)-3,8-diazabicyclo[3.2.1]octane hydrochlorideHCID 57882183Methanesulfonic Acid 4-(2,2,2-trifluoro-acetylamino)-butyl Ester

Product 1

HCID 18545195N-{4-[3-(4-Chloro-phenyl)-3,8-diaza-bicyclo[3.2.1]oct-8-yl]-butyl}-2,2,2-trifluoro-acetamideYield 39%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

3-(4-Chloro-phenyl)-3,8-diaza-bicyclo[3.2.1] octane hydrochloride salt (1.5 g, 5.79 mmol), triethylamine (1.77 mL, 12.73 mmol) and methanesulfonic acid 4-(2,2,2-trifluoro-acetylamino)-butyl ester (2.29 g, 8.68 mmol) were combined in tetrahydrofuran (25 mL). The resulting white heterogeneous reaction was heated at reflux for 24 hours. The mixture was cooled diluted with saturated sodium bicarbonate (200 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (200 mL), dried with magnesium sulfate and concentrated to a light brown oil. Silica gel flash chromatography using 5% methanol/ chloroform as eluent yielded N-{4-[3-(4-Chloro-phenyl)-3,8-diaza-bicyclo[3.2.1]oct-8-yl]-butyl}-2,2,2-trifluoro-acetamide (0.88 9, 39%) as an off-white solid which had the following properties: Mp. 83-85° C., 1H NMR CDCl3 δ: 7.77 (brd s, 1H), 7.16 (d, J=9.1 Hz, 2H), 6.68 (d, J=9.1 Hz, 2H), 3.44-3.35 (m, 4H), 3.29 (d, J=9.6 Hz, 2H), 3.02 (d, J=9.6 Hz, 2H), 2.51 (t, J=6.2 Hz, 2H), 2.10-1.90 (m, 2H), 1.83-1.76 (m, 2H), 1.73-1.57 (m, 6H).

Workup

  1. customThe resulting white heterogeneous reaction
  2. temperaturewas heated
  3. temperatureat reflux for 24 hours
  4. temperatureThe mixture was cooled
  5. extractionextracted with ethyl acetate (3×100 mL)
  6. washThe combined organic layers were washed with brine (200 mL)
  7. dry with materialdried with magnesium sulfate
  8. concentrationconcentrated to a light brown oil

Sources & evidence

ORD record
ord-f92fc2e4346c49fc9f62392df574cf6a
Source dataset
uspto-grants-2003_04
Patent number
US06552015B2

Reaction notes

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