4-(4-Methoxyphenyl)butyraMide synthesis

6synthesis methods

Product Name:4-(4-Methoxyphenyl)butyraMide
CAS Number:2222-15-3
Molecular formula:C11H15NO2
Molecular Weight:193.24

4521-28-2 Synthesis

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2222-15-3
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Yield:2222-15-3 97%

Reaction Conditions:

with 4-methyl-morpholine;sodium chloride;ammonia in tetrahydrofuran;methanol;ethyl acetate;

Steps:

4 4-(4-Methoxyphenyl)butyramide (117)

4-(4-Methoxyphenyl)butyramide (117)
4-(4-Methoxyphenyl) butyric acid (1) (450 g, 2.32 mole) was combined with dry THF (4 L) and 4-methylmorpholine (268 mL, 2.43 mole) in a 12 L three neck flask with mechanical stirring, an ice-methanol cooling bath and nitrogen atmosphere.
Small pieces of dry ice were used to bring the bath temperature below -20° C.
Isobutyl chloroformate was added at a rate so as not to exceed an internal temperature of -10° C.
After stirring for 30 min. at -10 to -20° C., a 4.7 M solution of ammonia in methanol (990 mL, 4.64 mole) was added in one portion.
During the addition, the reaction temperature rose to 0° C.
The reaction was allowed to stir for 30 min. and then allowed to stand overnight.
The product mixture was transferred to a 22 L separatory funnel with ethyl acetate (6 L), and 10% sodium chloride solution (1.5 L).
The layers were separated and the organic solution was washed with 10% sodium chloride solution (4*1 L) and then brine (3*500 mL).
The organic layer was dried over sodium sulfate, filtered, evaporated and placed under high vacuum overnight.
This afforded 432 g (97%) of the pure amide (117) as an off white solid.
¹H NMR (300 MHz, CD₃OD) δ 1.81-1.93 (m, 2H), 2.20 (t, J=7.7 Hz, 2H), 2.57 (t, J-7.7 Hz, 2H), 3.74 (s, 3H), 6.82 (d, J=8.7 Hz), 7.09 (d, J=8.7 Hz, 1H). CI MS m/z=194 [C₁₁H₁₅NO₂+H]⁺.