Dimethylformamide → (S)-tert-butyl 1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylcarbamate

HRID 407903Notes

Reaction equation

HRID 407903 reaction equation
CI.[CH2:3]([C:5]1[CH:6]=[N:7][C:8]([N:11]2[CH2:16][CH2:15][CH:14]([NH:17][C:18](=[O:32])[C@@H:19]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH2:21]SC)[CH2:13][CH2:12]2)=[N:9][CH:10]=1)[CH3:4].[H-].[Na+].CN(C=O)C.[Cl-].[NH4+]>C(Cl)Cl>[CH2:3]([C:5]1[CH:6]=[N:7][C:8]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:21][CH2:20][C@H:19]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:18]3=[O:32])[CH2:13][CH2:12]2)=[N:9][CH:10]=1)[CH3:4]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86688086(S)-tert-butyl 1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-ylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate methyliodide

Product 1

HCID 86688087(S)-tert-butyl 1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylcarbamateYield 68.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-ylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate methyliodide (7 g, 12 mmol) in CH2Cl2 (70 mL) was added 60% NaH in oil (580 mg, 14 mmol). After 5 minutes, DMF (7 mL) was added and the mixture stirred at ambient temperature for 1 hour. The mixture was poured into saturated ammonium chloride (70 mL) and the solution was extracted with CH2Cl2 (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting oil was triturated with ether (100 mL) and the ether layer was washed with brine. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to yield (S)-tert-butyl 1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-ylcarbamate (3.2 g, 8.2 mmol, 68%).

Workup

  1. extractionthe solution was extracted with CH2Cl2 (3×100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting oil was triturated with ether (100 mL)
  7. washthe ether layer was washed with brine
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-26f86ed28f074e678df820e793f2253d
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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