Lithium diisopropylamide → N-methoxy-N-methyl-3-(3-cyclopentyloxy-4-methoxyphenyl)prop-2-enamide

HRID 1871531Notes

Reaction equation

HRID 1871531 reaction equation
C(OP([CH2:9][C:10](=[O:15])[N:11]([O:13][CH3:14])[CH3:12])(=O)OCC)C.C([N-]C(C)C)(C)C.[Li+].[CH:24]1([O:29][C:30]2[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=2[O:38][CH3:39])[CH:33]=O)[CH2:28][CH2:27][CH2:26][CH2:25]1>O1CCCC1.O>[CH3:14][O:13][N:11]([CH3:12])[C:10](=[O:15])[CH:9]=[CH:33][C:32]1[CH:35]=[CH:36][C:37]([O:38][CH3:39])=[C:30]([O:29][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:31]=1

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 27358933-Cyclopentyloxy-4-methoxybenzaldehydeHCID 2773719Diethyl (N-methoxy-N-methylcarbamoylmethyl)phosphonate

Product 1

HCID 54075299N-methoxy-N-methyl-3-(3-cyclopentyloxy-4-methoxyphenyl)prop-2-enamideYield 95.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diethyl(N-methoxy-N-methyl-carbamoylmethyl)phosphonate (2.60 g, 10.90 mmol) in dry tetrahydrofuran (50 ml) at -78° C. was added lithium diisopropylamide (1.5M solution in cyclohexane, 7.33 ml, 11 mmol) dropwise over 3 minutes. The resulting solution was stirred at -78° C. for 30 minutes, after which time 3-cyclopentyloxy-4-methoxybenzaldehyde (1.5 g, 6.81 mmol) in dry tetrahydrofuran (5 ml) was added in one portion. The reaction was allowed to warm to room temperature and stirring continued overnight. After which time the reaction mixture was diluted with water (25 ml) and the tetrahydrofuran removed in vacuo. The aqueous residue was diluted with brine (25 ml) and extracted with methylene chloride (3×60 ml). The organic extracts were dried (Na2SO4) and evaporated in vacuo to give a yellow liquid. The liquid was purified by flash chromatography (SiO2 ; hexane/ethyl acetate (65:35)) to afford the title compound as a pale yellow liquid (1.986 g).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirring continued overnight
  3. customthe tetrahydrofuran removed in vacuo
  4. additionThe aqueous residue was diluted with brine (25 ml)
  5. extractionextracted with methylene chloride (3×60 ml)
  6. dry with materialThe organic extracts were dried (Na2SO4)
  7. customevaporated in vacuo
  8. customto give a yellow liquid
  9. customThe liquid was purified by flash chromatography (SiO2 ; hexane/ethyl acetate (65:35))

Sources & evidence

ORD record
ord-0153198dec1941f3aecec2bd4eb60fa3
Source dataset
uspto-grants-2000_08
Patent number
US06103749

Reaction notes

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