Tetrahydrofuran → cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane

HRID 2288762ノート

反応式

HRID 2288762 の反応式
C([N:8]1[CH2:15][C@@H:14]2[C@@H:10]([CH2:11][N:12]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:17]=3[F:25])[CH2:13]2)[CH2:9]1)C1C=CC=CC=1.C1COCC1.C([O-])=O.[NH4+]>[Pd].CO>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([N:12]2[CH2:11][C@@H:10]3[C@@H:14]([CH2:15][NH:8][CH2:9]3)[CH2:13]2)=[C:17]([F:25])[CH:18]=1

参加物

6

反応物 3

HCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 21969626cis-3-Benzyl-7-(2-fluoro-4-nitrophenyl)-3,7-diazabicyclo[3,3,0]octane

生成物 1

HCID 70202150cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 887Methanol溶媒

実験手順

cis-3-Benzyl-7-(2-fluoro-4-nitrophenyl)-3,7-diazabicyclo[3.3.0]octane (9.11 g, 26.71 mmol), THF (100 mL), and methanol (50 mL) are combined with 10% palladium on carbon (6.67 g) and ammonium formate (16.83 g, 266.90 mmol) under nitrogen, heated to reflux for 2.5 hours, cooled to ambient temperature, stirred 15 hours, filtered through celite and concentrated in vacuo to give crude cis-3-(4-amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane. cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane, water (100 mL), acetone (100 mL), and potassium carbonate (7.75 g, 56.07 mmol) are combined, cooled to 0° C., and benzyl chloroformate is added slowly. The reaction is warmed to ambient temperature, stirred 15 hours, concentrated in vacuo, and diluted with ethyl acetate. The organic phase is washed with water (2×150 mL) and saline (150 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with hexane/ethyl acetate (80/20). The appropriate fractions are combined (Rf =0.41, TLC, hexane/ethyl acetate, 50/50) and concentrated in vacuo to give the title compound, mp 121-122° C.

後処理

  1. temperatureheated
  2. temperatureto reflux for 2.5 hours
  3. filtrationfiltered through celite and
  4. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-cc8398273f7c47ee850ce4b94eaef61a
出典データセット
uspto-grants-2000_07
特許番号
US06090820

反応ノート

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