Ammonia → 3-Methoxybenzamide

HRID 705054Notes

Reaction equation

HRID 705054 reaction equation
C(C1OC(C(C2OC(CC)=CC=2)[C:9]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:10]=2[C:11](O)=[O:12])=CC=1)C.C1([N:33]=C=NC2CCCCC2)CCCCC1.N>ClCCl>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][CH:9]=[C:10]([CH:14]=1)[C:11]([NH2:33])=[O:12]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 10868DicyclohexylcarbodiimideHCID 711862912-[Bis(5-ethyl-2-furyl)methyl]-5-methoxybenzoic acid

Product 1

HCID 984873-MethoxybenzamideYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under argon, 2-formyl-5-methoxybenzoic acid (10 mmol) and 2-ethylfuran (40 mmol) were dissolved in abs. dioxane (20 ml), and after 10 minutes of stirring at room temperature, conc. perchloric acid (0.3 ml) was added. The resulting reaction mixture was subsequently stirred at 60° C. for 1 h, then poured into water and stirred. Filtration and drying of the resulting precipitate gave 2-[bis(5-ethyl-2-furyl)methyl]-5-methoxybenzoic acid in the form of a colourless solid (60% of theory). 2-[Bis(5-ethyl-2-furyl)methyl]-5-methoxybenzoic acid (10 mmol), dicyclohexylcarbodiimide (2.27 g, 11 mmol) were dissolved in abs. dichloromethane (90 ml) and stirred at room temperature for 10 min. Aqueous ammonia (4 ml) was then added, and the resulting reaction mixture was then stirred at room temperature for 1 h. Filtration, concentration under reduced pressure and subsequent purification by column chromatography (gradient ethyl acetate/n-heptane) of the residue that remained gave 2-[bis(5-ethyl-2-fury))methyl]-5-methoxybenzamide (982 mg, 28% of theory) in the form of a colourless solid. Under argon, abs. 1,2-dichloroethane (10 ml) was added to 2-[bis(5-ethyl-2-furyl)methyl]-5-methoxybenzamide (706 mg, 2 mmol) and p-toluenesulphonic acid bound to macroporous polystyrene resin (2 mmol). The resulting reaction mixture was stirred at a temperature of 100° C. for 1 h, after cooling to room temperature filtered off through Celite and concentrated under reduced pressure. Purification of the residue that remained by column chromatography (gradient ethyl acetate/n-heptane) gave 2,4-diethyl-10-methoxy-6,7-dihydro-8H-furo[2′,3′:3,4]cyclohepta[1,2-c]isoquinolin-8-one (51 mg, 8% of theory) in the form of a colourless solid. 1H-NMR (400 MHz, d6-DMSO δ, ppm) 11.66 (br. s, 1H, NH), 8.31 (d, 1H), 7.68 (d, 1H), 7.38 (dd, 1H), 6.47 (s, 1H), 5.35 (t, 1H), 3.87 (s, 3H), 2.79 (q, 2H), 2.68 (m, 2H), 2.33 (q, 2H), 1.30 (t, 3H), 0.96 (t, 3H).

Workup

  1. customthe resulting reaction mixture
  2. filtrationFiltration, concentration
  3. customunder reduced pressure and subsequent purification by column chromatography (gradient ethyl acetate/n-heptane) of the residue that

Sources & evidence

ORD record
ord-b3897de38c3e47cfa645907daf59dc80
Source dataset
uspto-grants-2015_11
Patent number
US09173395B2

Reaction notes

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