Tetrahydrofuran → (2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

HRID 227940Notes

Reaction equation

HRID 227940 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:32][C:33]([N:35]1[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]1[C:41]#[N:42])=[O:34])[C:12]12[CH2:19][CH2:18][C:15]([C:20](ON3C4C=CC=CC=4N=N3)=[O:21])([CH2:16][CH2:17]1)[CH2:14][CH2:13]2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:43]1[CH2:47][CH2:46][CH2:45][CH2:44]1.O1CCC[CH2:49]1>>[CH2:1]([O:8][C:9]([N:11]([CH2:32][C:33]([N:35]1[CH2:39][C@@H:38]([F:40])[CH2:37][C@H:36]1[C:41]#[N:42])=[O:34])[C:12]12[CH2:13][CH2:14][C:15]([C:20]([N:43]3[CH2:47][CH2:46][CH2:45][CH2:44][CH2:49]3)=[O:21])([CH2:18][CH2:19]1)[CH2:16][CH2:17]2)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 31268PyrrolidineHCID 57756828(2S,4S)-1-[(N-benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Product 1

HCID 68844891(2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile

Procedure

(2S,4S)-1-[[N-Benzyloxycarbonyl-N-[4-(benzotriazol-1-yl)oxycarbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (20.0 mg) and pyrrolidine (4.4 μL) were dissolved in tetrahydrofuran (0.4 mL) and the mixture was stirred at room temperature for 25 minutes. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane. The organic layer washed sequentially with 0.1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine. The organic layer was then dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluant:ethyl acetate:methanol=20:1) to give (2S,4S)-1-[[N-benzyloxycarbonyl-N-[4-(piperidin-1-yl)carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (16.0 mg).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washThe organic layer washed sequentially with 0.1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine
  4. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  5. concentrationwas concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel chromatography (eluant:ethyl acetate:methanol=20:1)

Sources & evidence

ORD record
ord-d38ef3ca138349b3840f0c6f352da442
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Reaction notes

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