Hydrochloric Acid → Ethyl 2-(1-(4-methoxy-3,5-dimethylphenylamino)cyclobutyl)acetate

HRID 2103079Notes

Reaction equation

HRID 2103079 reaction equation
[CH3:1][O:2][C:3]1[C:9]([CH3:10])=[CH:8][C:6]([NH2:7])=[CH:5][C:4]=1[CH3:11].[C:12]1(=[CH:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][CH2:14][CH2:13]1.Cl>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[C:4]([CH3:11])=[CH:5][C:6]([NH:7][C:12]2([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][CH2:14][CH2:13]2)=[CH:8][C:9]=1[CH3:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 41660974-Methoxy-3,5-dimethylanilineHCID 15724666Cyclobutylidene-acetic acid ethyl ester

Product 1

HCID 69053175Ethyl 2-(1-(4-methoxy-3,5-dimethylphenylamino)cyclobutyl)acetateYield 10.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 4-methoxy-3,5-dimethylaniline (5 g) and ethyl 2-cyclobutylideneacetate (10 g) in 6 mL toluene, under nitrogen was added by syringe 1mL HCl (4M in dioxane). After refluxing the solution for 3 days, the mixture was concentrated, water was added, and the solution was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over Na2SO4 and the solvent was removed by evaporation. The crude compound was purified by column chromatography (10% ethyl acetate/hexane), giving ethyl 2-(1-(4-methoxy-3,5-dimethylphenylamino)-cyclobutyl)acetate (1 g) as a while solid. 1H-NMR (300 MHz, CDCl3) δ=6.21 (s, 2H), 4.10(q, 2H), 3.67 (s, 3H), 2.90 (s, 2H), 2.33 (m, 2H), 2.19 (m, 8H), 1.95 (m, 2H), 1.24 (t, J =6.9 Hz, 3H) ppm. MS: m/z 293 (100, M+H)+

Workup

  1. temperatureAfter refluxing the solution for 3 days
  2. concentrationthe mixture was concentrated
  3. additionwater was added
  4. extractionthe solution was extracted with ethyl acetate (3×20 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. customthe solvent was removed by evaporation
  7. customThe crude compound was purified by column chromatography (10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c8a27e65e02848b9b8120778826d33aa
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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