Sodium hydride → (e)-3-Benzo[b]thiophen-3-yl-n-methoxy-n-methyl-acrylamide

HRID 2416279Notes

Reaction equation

HRID 2416279 reaction equation
CCOP(OCC)([CH2:6][C:7]([N:9]([O:11][CH3:12])[CH3:10])=[O:8])=O.[H-].[Na+].[S:18]1[CH:22]=[C:21]([CH:23]=O)[C:20]2[CH:25]=[CH:26][CH:27]=[CH:28][C:19]1=2>C1COCC1>[S:18]1[CH:22]=[C:21](/[CH:23]=[CH:6]/[C:7]([N:9]([O:11][CH3:12])[CH3:10])=[O:8])[C:20]2[CH:25]=[CH:26][CH:27]=[CH:28][C:19]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2273281-Benzothiophene-3-carbaldehydeHCID 2773719Diethyl (N-methoxy-N-methylcarbamoylmethyl)phosphonate

Product 1

HCID 22638837(e)-3-Benzo[b]thiophen-3-yl-n-methoxy-n-methyl-acrylamideYield 93.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl (N-methoxy-N-methylcarbamoylmethyl)phosphonate (6.13 g, 25.6 mmol) was added dropwise via syringe to a stirred suspension of sodium hydride (1.02 g, 25.6 mmol) in anhydrous THF (75 ml) at 0° C. The reaction was warmed to room temperature and was stirred for 1 h. After cooling to 0° C., benzo[b]thiophene-3-carbaldehyde (3.78 g, 23.3 mmol) was added. The resulting mixture was stirred at room temperature for 1 hr. The reaction was quenched with 100 mL aqueous HCl (0.1 N) and extracted with ethyl acetate (250 ml). The combined organic layers were washed with brine (50 ml) and dried over anhydrous magnesium sulfate. The filtrate was concentrated in vacuo and triturated with hexane to give (E)-3-benzo[b]thiophen-3-yl-N-methoxy-N-methyl-acrylamide (5.38 g, 93%) as a yellow solid. 1H NMR (500 MHz, CDCl3) 8.06-8.01 (2H, 2 superimposed d, J=8.24, 15.87 Hz), 7.89 (1H, d, J=7.94 Hz), 7.78 (1H, s), 7.47 (1H, t, J=7.93 Hz), 7.41 (1H, t, J=8.24 Hz), 7.13 (1H, d, J=15.87 Hz), 3.79 (3H, s), 3.34 (3H, s); MS m/e 248.07 (M+H)+.

Workup

  1. temperatureAfter cooling to 0° C.
  2. stirringThe resulting mixture was stirred at room temperature for 1 hr
  3. customThe reaction was quenched with 100 mL aqueous HCl (0.1 N)
  4. extractionextracted with ethyl acetate (250 ml)
  5. washThe combined organic layers were washed with brine (50 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationThe filtrate was concentrated in vacuo
  8. customtriturated with hexane

Sources & evidence

ORD record
ord-f9b70ac73977458993f6fd5d2961544a
Source dataset
uspto-grants-2004_11
Patent number
US06822100B2

Reaction notes

Loading…