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

HRID 352374

반응식

HRID 352374 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 82844Platinum oxide (PtO)촉매HCID 176Acetic Acid용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c57e387d19ef486fae8e1570993205d2
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06747022B2

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