Pyridine → [4-(3-Aza-bicyclo[3.1.0]hex-3-yl)-3,5-difluoro-phenyl]-carbamic acid benzyl ester

HRID 1814031ノート

反応式

HRID 1814031 の反応式
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([F:11])[C:3]=1[N:12]1[CH2:17][CH:16]2[CH:14]([CH2:15]2)[CH2:13]1.[Cl-].[NH4+].N1C=CC=CC=1.Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]>C(O)C.O.ClCCl.[Fe]>[CH2:30]([O:29][C:27](=[O:28])[NH:8][C:6]1[CH:7]=[C:2]([F:1])[C:3]([N:12]2[CH2:17][CH:16]3[CH:14]([CH2:15]3)[CH2:13]2)=[C:4]([F:11])[CH:5]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

参加物

8

反応物 4

HCID 1049PyridineHCID 10387Benzyl chloroformateHCID 25517Ammonium ChlorideHCID 114249713-(2,6-Difluoro-4-nitro-phenyl)-3-aza-bicyclo[3.1.0]hexane

生成物 1

HCID 11290870[4-(3-Aza-bicyclo[3.1.0]hex-3-yl)-3,5-difluoro-phenyl]-carbamic acid benzyl ester

試薬・触媒・溶媒 3

HCID 23925Iron触媒HCID 6344Dichloromethane溶媒2 回HCID 19096565Water ethanol溶媒

反応条件

温度
0 °C

実験手順

Iron metal (0.120 g, 2.15 mmol) was added in five portions over 1 h to a refluxing solution of 3-(2,6-difluoro-4-nitro-phenyl)-3-aza-bicyclo[3.1.0]hexane (0.172 g, 0.72 mmol) and ammonium chloride (0.385 g, 7.2 mmol) in 6.0 mL of 2:1 ethanol-H2O. The rust colored mixture was refluxed for another 30 min and then cooled and filtered to remove iron oxide. H2O was added to the filtrate and the mixture concentrated to remove ethanol. The resulting aqueous solution was extracted with three 20 mL portions of ethyl acetate and the combined organic phases washed with H2O, brine, and dried (MgSO4). Filtration and concentration gave the crude amine (0.145 g, 0.69 mmol) which was dissolved in 5.0 mL of dichloromethane. Pyridine (0.111 mL, 1.38 mmol) was added to the amine solution and after cooling to 0° C., benzyl chloroformate (0.113 mL, 0.79 mmol) was added. The mixture was stirred for 30 min at 0° C. and for 30 min at room temperature. The reaction mixture was then diluted with dichloromethane and washed with H2O, brine and then dried (MgSO4). Concentration gave a yellow oil that was triturated with hexane to afford [4-(3-aza-bicyclo[3.1.0]hex-3-yl)-3,5-difluoro-phenyl]-carbamic acid benzyl ester as a yellow solid.

後処理

  1. temperaturecooled
  2. filtrationfiltered
  3. customto remove iron oxide
  4. additionH2O was added to the filtrate
  5. concentrationthe mixture concentrated
  6. customto remove ethanol
  7. extractionThe resulting aqueous solution was extracted with three 20 mL portions of ethyl acetate
  8. washthe combined organic phases washed with H2O, brine
  9. dry with materialdried (MgSO4)
  10. filtrationFiltration and concentration
  11. customgave the crude amine (0.145 g, 0.69 mmol) which
  12. washwashed with H2O, brine
  13. dry with materialdried (MgSO4)
  14. concentrationConcentration
  15. customgave a yellow oil that
  16. customwas triturated with hexane

出典と根拠

ORDレコード
ord-5986c531e27e46c8a7149993dc49a98d
出典データセット
uspto-grants-2005_04
特許番号
US06875784B2

反応ノート

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