Imidazole → HCID 86660283, compound

HRID 1631044Notes

Reaction equation

HRID 1631044 reaction equation
[Cl:1][C:2]1[C:3]([N:10]2[CH2:14][C@H:13]([OH:15])[CH2:12][C@H:11]2[C:16]([O:18][CH3:19])=[O:17])=[N:4][CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.N1C=CN=C1.[Si:25](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]>CN(C=O)C.CCOC(C)=O>[Si:25]([O:15][C@H:13]1[CH2:14][N:10]([C:3]2[C:2]([Cl:1])=[CH:7][C:6]([C:8]#[N:9])=[CH:5][N:4]=2)[C@H:11]([C:16]([O:18][CH3:19])=[O:17])[CH2:12]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 86660284HCID 86660284, compound

Product 1

HCID 86660283HCID 86660283, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl (2S,4R)-1-(3-chloro-5-cyanopyridin-2-yl)-4-hydroxypyrrolidine-2-carboxylate (0.270 g; 0.96 mmol) and imidazole (0.098 g; 1.44 mmol) in DMF (3 mL) was added tert-butyl dimethylsilylchloride (0.159 g; 1.05 mmol). The reaction mixture was stirred at ambient temperature for 18 hours. Further imidazole (0.049 g; 0.72 mmol) and tert-butyldimethylsilyl chloride (0.080 g; 0.53 mmol) was added and the reaction stirred at ambient temperature for 3 hours. The reaction mixture was diluted with EtOAc and washed sequentially with water and brine. The organic phase was poured through a hydrophobic frit and the solvent evaporated in vacuo. The residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (6:1) to afford the title product (0.311 g, 82%). 1H NMR (CDCl3, 400 MHz) δ 8.16 (1H, d, J=2 Hz), 7.57 (1H, d, J=2 Hz), 4.79 (1H, t, J=8 Hz), 4.46-4.44 (1H, m), 4.17-4.13 (1H, dd, J=11.2, 4.8 Hz), 3.77-3.74 (1H, m), 3.63 (3H, s), 2.15 (1H, m), 1.96 (1H, m), 0.79 (9H, s), 0.14-0.02 (6H, m).

Workup

  1. stirringthe reaction stirred at ambient temperature for 3 hours
  2. washwashed sequentially with water and brine
  3. additionThe organic phase was poured through a hydrophobic frit
  4. customthe solvent evaporated in vacuo
  5. customThe residue was purified by flash chromatography on silica
  6. washeluting with iso-hexane/EtOAc (6:1)

Sources & evidence

ORD record
ord-9e96babf51614f5e808c1642a1f5ab6a
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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