1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[(3S)-4-[4-[1-(benzyloxycarbonyl)-4-piperidyloxy]phenyl]-3-(t-butoxycarbonylamino)-1-butenyl]benzonitrile

HRID 747761Notes

Reaction equation

HRID 747761 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([CH2:24][C@H:25]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:26](OC)=O)=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+].[Br-].[C:61]([C:63]1[CH:64]=[C:65]([CH:86]=[CH:87][CH:88]=1)[CH2:66][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)#[N:62].C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1.CCCCCC.C(O)C.O1CCCC1.C(OCC)(=O)C.CO>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([O:17][C:18]2[CH:19]=[CH:20][C:21]([CH2:24][C@H:25]([NH:30][C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH:26]=[CH:66][C:65]3[CH:64]=[C:63]([CH:88]=[CH:87][CH:86]=3)[C:61]#[N:62])=[CH:22][CH:23]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

12

Reactant 5

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2778355(3-Cyanobenzyl)triphenylphosphonium bromideHCID 9855836Potassium sodium tartarateHCID 21225700DiisobutylaluminumhydrideHCID 86760707methyl (2S)-3-[4-[1-(benzyloxycarbonyl)-4-piperidyloxy]phenyl]-2-(t-butoxycarbonylamino)propionate

Product 1

HCID 688292673-[(3S)-4-[4-[1-(benzyloxycarbonyl)-4-piperidyloxy]phenyl]-3-(t-butoxycarbonylamino)-1-butenyl]benzonitrile

Reagents, catalysts & solvents 6

HCID 702EthanolSolventHCID 887MethanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3.87 g (7.70 mmol) of methyl (2S)-3-[4-[1-(benzyloxycarbonyl)-4-piperidyloxy]phenyl]-2-(t-butoxycarbonylamino)propionate was dissolved in 77 ml of toluene. 19.3 ml (19.3 mmol) of 1.0 M solution of diisobutylaluminum hydride in hexane was added to the obtained solution at −78° C., and they were stirred for 10 minutes. 10 ml of methanol and 20 ml of saturated aqueous solution of potassium sodium tartrate were added to the resultant mixture, and they were stirred at room temperature for additional one hour. After the treatment with ethyl acetate as the extractant in an ordinary manner, the obtained oily residue was dissolved in a mixed solvent of 30 ml of ethanol and 30 ml of tetrahydrofuran. After the addition of 3.53 g (7.70 mmol) of (3-cyanobenzyl)triphenylphosphonium bromide and 1.15 ml (7.70 mmol) of DBU at room temperature, the resultant mixture was stirred for one hour. The solvent was distilled off under reduced pressure, and the residue was purified by the silica gel column chromatography to obtain the title compound in the form of a mixture of geometrical isomers (E:Z=2:3).

Workup

  1. stirringwere stirred at room temperature for additional one hour
  2. distillationThe solvent was distilled off under reduced pressure
  3. customthe residue was purified by the silica gel column chromatography

Sources & evidence

ORD record
ord-4e06595449764e2695d12705312d0ac0
Source dataset
uspto-grants-2008_07
Patent number
US07396844B1

Reaction notes

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