Sodium hydride → (S)-1-tert-Butyl 2-methyl 4-(cyanomethylene)pyrrolidine-1,2-dicarboxylate

HRID 1745000Notes

Reaction equation

HRID 1745000 reaction equation
CCOP(OCC)([CH2:6][C:7]#[N:8])=O.[H-].[Na+].O=[C:15]1[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:17]([C:27]([O:29][CH3:30])=[O:28])[CH2:16]1.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[C:7]([CH:6]=[C:15]1[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:17]([C:27]([O:29][CH3:30])=[O:28])[CH2:16]1)#[N:8]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 109884851-tert-butyl 2-methyl (2S)-4-oxopyrrolidine-1,2-dicarboxylate

Product 1

HCID 118308474(S)-1-tert-Butyl 2-methyl 4-(cyanomethylene)pyrrolidine-1,2-dicarboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Diethyl cyanomethyl phosphonate (0.86 ml, 4.4 mmol) was dissolved in dry THF (50 ml) and the solution cooled to 0° C. Sodium hydride (205 mg of a 60% suspension in parrafin oil, 5.1 mmol) was then added cautiously and the reaction stirred for 30 min. The reaction mixture was then cooled to −78° C. and a solution of 1-tert-butyl 2-methyl (2S)-4oxo-1,2-pyrrolidinedicarboxylate (1.0 g, 4.1 mmol) in dry THF (5 ml) was added dropwise. The reaction was then allowed to reach room temperature. Saturated aqueous ammonium chloride solution (15 ml) was then added, followed by ethyl acetate (100 ml). (The organic layer was removed, and the aqueous washed with ethyl acetate (3×5 ml). The combined organic layers were dried with brine and magnesium sulfate before filtering and removal of solvent. Silica gel chromatography, eluting with 35% ethyl acetate in hexanes gave the desired compound (860 mg, 80%) as an off-white wax.

Workup

  1. temperatureThe reaction mixture was then cooled to −78° C.
  2. customto reach room temperature
  3. custom(The organic layer was removed
  4. washthe aqueous washed with ethyl acetate (3×5 ml)
  5. dry with materialThe combined organic layers were dried with brine and magnesium sulfate
  6. filtrationbefore filtering
  7. customremoval of solvent
  8. washSilica gel chromatography, eluting with 35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-742a2f0977154b969fc65f2bda53bf84
Source dataset
uspto-grants-2006_03
Patent number
US07018988B2

Reaction notes

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