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

HRID 1266985ノート

反応式

HRID 1266985 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f92fc2e4346c49fc9f62392df574cf6a
出典データセット
uspto-grants-2003_04
特許番号
US06552015B2

反応ノート

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