Diisopropylethylamine → (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile

HRID 555680

Reaction equation

HRID 555680 reaction equation
[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(N(C(C)C)CC)(C)C.Br[CH2:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[C:33]#[N:34])=[O:27]>CN(C)C=O>[CH2:13]([O:12][C:10]([C:5]12[CH2:4][CH2:3][C:2]([NH:1][CH2:25][C:26]([N:28]3[CH2:32][CH2:31][CH2:30][C@H:29]3[C:33]#[N:34])=[O:27])([CH2:9][CH2:8]1)[CH2:7][CH2:6]2)=[O:11])[CH3:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11031276(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonitrileHCID 23149693Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate

Product 1

HCID 59383131(2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrileYield 51.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (115 mg) was dissolved in N,N-dimethylformamide (1.5 mL) and diisopropylethylamine (100 μL) was added to the solution. (2S)-1-(2-Bromoacetyl)pyrrolidine-2-carbonitrile (120 mg) in N,N-dimethylformamide (1 mL) was then added dropwise at room temperature. The mixture was stirred for 2 hours at room temperature and was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant:chloroform:methanol=10:1) to give (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (95.1 mg).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customThe residue was purified by silica gel column chromatography (eluant:chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-df5d7235011248d1a2dd7864f1328019
Source dataset
uspto-grants-2011_11
Patent number
US08053465B2

Linked notes

Loading…