Sodium hydride → HCID 54350758, compound

HRID 1432882Notes

Reaction equation

HRID 1432882 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH:6]([P:15](=[O:22])([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18])P(=O)(OCC)OCC)[CH3:5].[Cl:23][C:24]1[S:28][C:27]([CH:29]=O)=[CH:26][CH:25]=1>C1COCC1>[CH2:20]([O:19][P:15]([C:6]([N:4]([CH3:3])[CH3:5])=[CH:29][C:27]1[S:28][C:24]([Cl:23])=[CH:25][CH:26]=1)(=[O:22])[O:16][CH2:17][CH3:18])[CH3:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 817002-Thiophenecarboxaldehyde, 5-chloro-HCID 86795Tetraethyl ((dimethylamino)methylene)bisphosphonate

Product 1

HCID 54350758HCID 54350758, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (0.25 g, 6.25 mmol, 60% mineral oil dispersion) in 10 mL of THF is added slowly a solution of tetraethyl dimethylaminomethylenediphosphonate (2.03 g, 6.14 mmol, prepared according to the procedure described in Psaume, Montury, and Cosmetic Comm. 1982, 12, 415) in 10 mL of THF. After stirring 1 h, a solution of 5-chloro-2-thiophene carboxaldehyde (0.90 g, 6.14 mmol) in 10 mL of THF is added. The resulting mixture is heated at reflux for 1 h, then cooled to room temperature. The reaction mixture is partitioned between Et2O and water. The organic layer is washed sequentially with 1N HCl, water and saturated NaCl, then dried over MgSO4, filtered and concentrated. The crude product is purified via flash column chromatography eluting with a gradient of 40% EtOAc/hexanes to 50% EtOAc/hexanes to afford the title compound (1.52 g, 4.69 mmol) as an oil. 1H NMR (CDCl3, 300 MHz) δ7.20 (d, 1H), 6.95 (d, 1H), 6.82 (d, 1H), 4.15 (m, 4H), 2.62 (s, 6H), 1.60 (t, 6H).

Workup

  1. customprepared
  2. temperatureThe resulting mixture is heated
  3. temperatureat reflux for 1 h
  4. customThe reaction mixture is partitioned between Et2O and water
  5. washThe organic layer is washed sequentially with 1N HCl, water and saturated NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified via flash column chromatography
  10. washeluting with a gradient of 40% EtOAc/hexanes to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-54efc10ab05d4df79be50323fc6564b4
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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