Hydrochloric Acid → (2S,4S)-1-[[N-Benzyloxycarbonyl-N-[4-carboxybicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227935Notes

Reaction equation

HRID 227935 reaction equation
C(N(C(C)C)C(C)C)C.[CH2:10]([O:17][C:18](Cl)=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O1CCCCC1[O:27][C:28]([C:30]12[CH2:37][CH2:36][C:33]([NH:38][CH2:39][C:40]([N:42]3[CH2:46][C@@H:45]([F:47])[CH2:44][C@H:43]3[C:48]#[N:49])=[O:41])([CH2:34][CH2:35]1)[CH2:32][CH2:31]2)=[O:29].Cl>O1CCOCC1.O>[CH2:10]([O:17][C:18]([N:38]([CH2:39][C:40]([N:42]1[CH2:46][C@@H:45]([F:47])[CH2:44][C@H:43]1[C:48]#[N:49])=[O:41])[C:33]12[CH2:36][CH2:37][C:30]([C:28]([OH:29])=[O:27])([CH2:35][CH2:34]1)[CH2:31][CH2:32]2)=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 59383132(2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2,2,2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Product 1

HCID 68842664(2S,4S)-1-[[N-Benzyloxycarbonyl-N-[4-carboxybicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Ethyldiisopropylamine (194 μL) and benzylchloroformate (137 μL) were added dropwise to (2S,4S)-1-[[N-[4-(2-tetrahydropyranyl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (379 mg) in dioxane (5 mL) while the solution was cooled in water. The mixture was stirred at room temperature for 1 hour, followed by addition of 1N hydrochloric acid (0.1 mL) and stirring at room temperature for additional 1 hour. The solvent was evaporated under reduced pressure. The resulting crystal was then washed with diisopropylether and water and was dried under reduced pressure. The dried crystal was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1) to give (2S,4S)-1-[[N-benzyloxycarbonyl-N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (335 mg).

Workup

  1. stirringstirring at room temperature for additional 1 hour
  2. customThe solvent was evaporated under reduced pressure
  3. washThe resulting crystal was then washed with diisopropylether and water
  4. customwas dried under reduced pressure
  5. customThe dried crystal was purified by silica gel chromatography (eluant:dichloromethane:methanol=10:1)

Sources & evidence

ORD record
ord-bc65bb5003f447799a231647faf59430
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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