Methane → (R)-(-)-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

HRID 352374

反応式

HRID 352374 の反応式
[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[NH:5][CH2:4][C@H:3]1[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].[C:21]1(=O)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.[H][H].C>C(O)(=O)C.[Pt]=O.C(OCC)(=O)C>[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH2:4][C@H:3]1[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

参加物

8

反応物 4

HCID 297MethaneHCID 7967CyclohexanoneHCID 12988641(R)-2-oxo-3-tert-butoxycarbonylamino-1,3,4,5-tetrahydro-2H-1,5-benzodiazepineHCID 178418361HCID 178418361、化合物

生成物 1

HCID 12043264(R)-(-)-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine収率 91.5%

試薬・触媒・溶媒 3

HCID 82844Platinum oxide (PtO)触媒HCID 176Acetic Acid溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 50 g of (R)-(+)-2-oxo-3-tert-butoxycarbonylamino-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine as described in WO98/25911 in 43.3 g of acetic acid were added 70.8 g of cyclohexanone and 1.5 g of platinum oxide. The resulting mixture was stirred at room temperature for 5 hours under pressure of 3 to 3.5 kg/cm2 in a hydrogen gas atmosphere. To the reaction mixture were added 200 ml of ethyl acetate and 5 g of active charcoal, followed by stirring for further 1 hour at room temperature. The reaction mixture was filtered. A 2N aqueous solution of sodium hydroxide was added dropwise to the filtrate to neutralize the same under stirring and then, it was separated into layers. The organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue were added 200 ml of ethanol and 200 ml of water. The mixture was stirred at 50° C. for 1 hour and then for 2 hours under ice cooling. Crystals so precipitated were collected by filtration with suction, washed with a mixed solvent of ethanol and water (1:1) and then dried to obtain 59.3 g of the title compound.

後処理

  1. filtrationThe reaction mixture was filtered
  2. additionA 2N aqueous solution of sodium hydroxide was added dropwise to the filtrate
  3. stirringunder stirring
  4. customit was separated into layers
  5. washThe organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. additionTo the residue were added 200 ml of ethanol and 200 ml of water
  9. stirringThe mixture was stirred at 50° C. for 1 hour
  10. waitfor 2 hours under ice cooling
  11. customCrystals so precipitated
  12. filtrationwere collected by filtration with suction
  13. washwashed with a mixed solvent of ethanol and water (1:1)
  14. customdried

出典と根拠

ORDレコード
ord-c57e387d19ef486fae8e1570993205d2
出典データセット
uspto-grants-2004_06
特許番号
US06747022B2

関連ノート

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