Ethyl Acetate → N-[4-(hydroxymethyl)phenyl]acrylamide

Temperature

0 °C

p-Aminobenzyl alcohol (12.31 g, 100 mmol) was dissolved in a mixture of dichloromethane (200 mL) and tetrahydrofuran (20 mL) containing N,N-diisopropylethylamine (35 mL, 200 mmol). The resulting homogeneous solution was then cooled to 0° C. and acryloyl chloride (8.2 mL, 100 mmol) was added drop-wise over a 30-minute period while keeping the internal temperature of the reaction mixture below 20° C. The reaction mixture was stirred at 0° C. for about 60 minutes. The reaction mixture was poured into ice-cold 1M hydrochloric acid (0.6 L) and the organic layer was separated and evaporated to dryness to give a crude material (5 g) consisting primarily of the bis-acylated side product. The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) and the combined ethyl acetate layers were dried with sodium sulfate, filtered and concentrated under reduced pressure to provide a residue. Trituration of the residue with ethyl acetate yielded the title compound (10.5 g, 98.5% pure). An additional 2 g of the title compound were obtained by trituration of the crude material obtained from the dichloromethane layer.

1. customthe internal temperature of the reaction mixture below 20° C
2. customthe organic layer was separated
3. customevaporated to dryness
4. customto give a crude material (5 g)
5. extractionThe acidic aqueous layer was then extracted with ethyl acetate (2×200 mL)
6. dry with materialthe combined ethyl acetate layers were dried with sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto provide a residue

ORD record

ord-3474fae1fe6e43e8ad57217245b1b17b

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247564B2