反応 #745324

ord-dbddcde10008464aa851938686eeb044

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    ろ過collected by suction filtration
  2. 2
    その他The resin obtained in this way
  3. 3
    workup.STIRRINGThe mixture is shaken at RT overnight
  4. 4
    ろ過The solid is collected by suction filtration
  5. 5
    洗浄washed three times each with 10 ml of dimethylformamide, methanol and dichloromethane
  6. 6
    ろ過collected by suction filtration
  7. 7
    workup.ADDITION20 ml of a 50% trifluoroacetic acid solution in dichloromethane are added
  8. 8
    workup.WAITleft
  9. 9
    workup.WAITto act for 60 min
  10. 10
    その他the resin is removed by filtration on a frit
  11. 11
    洗浄the resin is washed three times with 10 ml of dichloromethane
  12. 12
    濃縮The filtrate is concentrated
  13. 13
    その他the target compound is obtained as crude product

実験手順

1 g (0.62 mmol) of a Wang resin (Merck Biosciences; loading: 0.62 mmol/g) preloaded with O-tert.-butyl-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-serine is treated twice in succession with piperidine as follows: the resin is mixed with 10 ml of a 20% piperidine solution in dimethylformamide, shaken for 30 min and collected by suction filtration. The resin obtained in this way is provided in 10 ml of dimethylformamide, and 369 mg (1.24 mmol) of N-[(9H-fluoren-9-ylmethoxy)carbonyl]glycine, 398 mg (1.24 mmol) of N-[(1H-benzotriazol-1-yloxy)(dimethyl-amino)methylene]-N-methylmethanaminium tetrafluoroborate (TBTU) and 240 mg (1.86 mmol) of N-ethyl-N-isopropylpropan-2-amine (DIEA) are added. The mixture is shaken at RT overnight. The solid is collected by suction filtration, washed three times each with 10 ml of dimethylformamide, methanol and dichloromethane and collected by suction filtration. 20 ml of a 50% trifluoroacetic acid solution in dichloromethane are added and left to act for 60 min, the resin is removed by filtration on a frit and the resin is washed three times with 10 ml of dichloromethane. The filtrate is concentrated and the target compound is obtained as crude product.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08076285B2uspto-grants-2011_12