Sodium hydride → HCID 69719929, compound

HRID 2308136Notes

Reaction equation

HRID 2308136 reaction equation
[H-].[Na+].[C:3]([CH2:5]P(=O)(OCC)OCC)#[N:4].[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[N+:30]([O-:32])=[O:31])[CH:25]=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([CH:25]=[CH:5][C:3]#[N:4])[CH:27]=[CH:28][C:29]=1[N+:30]([O-:32])=[O:31])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 12111719HCID 12111719, compound

Product 1

HCID 69719929HCID 69719929, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

3-Hydroxy-4-nitrobenzaldehyde (2) (4.18 g, 25 mmol) was dissolved in anhydrous DMF (100 mL). To this solution was added benzyl bromide (3.27 mL, 27.5 mmol) and potassium carbonate (3.8 g, 27.5 mmol). The reaction mixture was stirred at room temperature for 18 h, filtered and evaporated. The residue was taken up into ethyl acetate (250 mL) and water (250 mL). The organic layer was washed with brine (50 mL), dried over MgSO4, filtered and evaporated leaving 3-benzyloxy-4-nitro-benzaldehyde (3) as an orange solid (6.31 g, 98% yield): 1HNMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.91 (s, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.45 (m, 5H), 5.40 (s, 2H); 13CNMR (400 MHz, DMSO-d6) δ 192.4, 151.2, 143.5, 139.9, 135.9, 128.9, 128.6, 127.9, 125.9, 122.7, 115.5, 71.1. To a suspension of sodium hydride (0.29 g, 12 mmol) in anhydrous THF (25 mL) at 0° C. was added via dropping funnel diethyl cyanomethylphosphonate (4) (1.94 mL, 12 mmol) in anhydrous THF (5 mL) followed by 3-benzyloxy-4-nitro-benzaldehyde (3) (2.6 g, 10 mmol) in anhydrous THF (30 mL). The reaction mixture was warmed up to room temperature and stirred for 2 h. The solvent was evaporated and the residue was taken up into ethyl acetate (50 mL) and water (25 mL). The organic phase was washed with brine (25 mL), dried over MgSO4, filtered and evaporated leaving 3-(3-benzyloxy-4-nitro-phenyl)-acrylonitrile (5) as an orange-red solid (0.28 g, 100% yield): 1HNMR (400 MHz, DMSO-d6) δ 8.04 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.71 (d, J=16.6 Hz, 1H), 7.45 (m, 6H), 6.72 (d, J=16.6 Hz, 1H), 5.33 (s, 2H); 13CNMR (400 MHz, DMSO-d6) δ 151.4, 148.9, 140.8, 139.5, 136.0, 128.9, 128.6, 128.0, 126.0, 120.7, 118.5, 114.5, 101.3, 71.1; MS calculated for C16H12N2O3 (M)+: 280. found 280. 3-(3-Benzyloxy-4-nitro-phenyl)-(5) (0.28 g, 1.0 mmol) was dissolved in anhydrous methanol (20 mL). To this solution was added 10% palladium on carbon (56 mg, 20% wt) under a blanket of carbon dioxide. The hydrogenation was carried out under 60 psi of hydrogen at room temperature for 4 h, filtered through a pad of Celite and evaporated to yield an orange oil. This oil was stirred in hexane, decanted and vacuum dried leaving 3-(4-amino-3-hydroxy-phenyl)-propionitrile (1) as an orange solid (0.58 g, 100% yield): 1HNMR (400 MHz, DMSO-d6) δ 8.81 (bs, 1H), 6.31 (m, 3H), 4.30 (bs 2H), 3.18 (s, 2H), 2.35 (s, 2H); 13CNMR (400 MHz, DMSO-d6) δ 144.3, 135.5, 127.1, 120.8, 119.6, 114.9, 30.5, 19.2; MS calculated for C9H10N2O (M)+: 162. found 162.

Workup

  1. additionwas added
  2. customThe solvent was evaporated
  3. washThe organic phase was washed with brine (25 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-b87c337bf2344ff690666bed15a42353
Source dataset
uspto-grants-2004_12
Patent number
US06835213B2

Reaction notes

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