Malononitrile → HCID 10716447, compound

HRID 1923995Notes

Reaction equation

HRID 1923995 reaction equation
[C:1](#[N:5])[CH2:2][C:3]#[N:4].CN(P(N(C)C)(N(C)C)=O)C.[H-].[Na+].I[CH2:20][C@H:21]([NH:26][C:27]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]([O:24][CH3:25])=[O:23]>C1COCC1>[C:3]([CH:2]([C:1]#[N:5])[CH2:20][C@H:21]([NH:26][C:27]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]([O:24][CH3:25])=[O:23])#[N:4]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 10648076HCID 10648076, compound

Product 1

HCID 10716447HCID 10716447, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of malononitrile (0.71 g; 10.6 mmol) in mixture of THF (30 mL) and HMPA (20 mL) was added sodium hydride 60% (0.43 g; 10.6 mmol) and stirred for min. To this mixture was added a solution of methyl (2R)-3-iodo-2-(tritylamino)propanoate CIII (5.0 g; 10.6 mmol) in THF (52 mL) and stirred overnight at r.t. The reaction was quenched with saturated aqueous ammonium chloride and extracted with diethyl ether (5×). The combined organic layers were washed with saturated aqueous ammonium chloride and dried over anhydrous MgSO4. The solvent was removed and the residue was purified on a silica gel column (3:1 hexane/EtOAc) and then crystallized from hexane/EtOAc to give the methyl (2S)-4,4-dicyano-2-(tritylamino)butanoate CIV (2.62 g; 6.4 mmol; 60% yield). 1H NMR (CDCl3) 3.02-3.06 (m, 1H), 2.70-2.75 (m, 1H), 2.81-2.86 (m, 1H), 2.95 (dd, J=12 Hz, J=6 Hz, 1H), 3.76 (s, 3H), 4.51 (d, J=6 Hz, 1H), 7.23 (t, J=8 Hz, 3H), 7.32 (dd, J=8 Hz, J=8 Hz, 6H), 7.43 (d, J=8 Hz, 6H); ESIMS found for C26H23N3O2 m/z 432.3 (M+Na).

Workup

  1. stirringstirred overnight at r.t
  2. customThe reaction was quenched with saturated aqueous ammonium chloride
  3. extractionextracted with diethyl ether (5×)
  4. washThe combined organic layers were washed with saturated aqueous ammonium chloride
  5. dry with materialdried over anhydrous MgSO4
  6. customThe solvent was removed
  7. customthe residue was purified on a silica gel column (3:1 hexane/EtOAc)
  8. customcrystallized from hexane/EtOAc

Sources & evidence

ORD record
ord-f39e62e85a8f4fb0852ac2413a350a0e
Source dataset
uspto-grants-2012_05
Patent number
US08178490B2

Reaction notes

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