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HuagongsheHuagongshe Chemistry Print Report · For research reference only
HRID 1366867Generated: November 1, 2026

3-Acetamidophthalic Anhydride → Apremilast, (+-)-

https://huagongshe.com/reaction/1366867

Reaction equation

Participants

RoleNameHCIDCharge
Reactant3-Acetamidophthalic AnhydrideHCID 226121—
Reactant1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamineHCID 11288792—
SolventAcetic AcidHCID 176—
ProductApremilast, (+-)-HCID 1015171559.3%

Reaction Steps

A stirred solution of 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (1.0 g, 3.7 mmol) and 3-acetamidophthalic anhydride (751 mg, 3.66 mmol) in acetic acid (20 mL) was heated at reflux for 15 h. The solvent was removed in vacuo to yield an oil. Chromatography of the resulting oil yielded the product as a yellow solid (1.0 g, 59% yield): mp, 144° C.; 1H NMR (CDCl3) δ: 1.47 (t, J=7.0 Hz, 3H, CH3), 2.26 (s, 3H, CH3), 2.88 (s, 3H, CH3), 3.75 (dd, J=4.4, 14.3 Hz, 1H, CH), 3.85 (s, 3H, CH3), 4.11 (q, J=7 Hz, 2H, CH2), 5.87 (dd, J=4.3, 10.5 Hz, 1H, NCH), 6.82-6.86 (m, 1H, Ar), 7.09-7.11 (m, 2H, Ar), 7.47 (d, J=7 Hz, 1H, Ar), 7.64 (t, J=8 Hz, 1H, Ar), 8.74 (d, J=8 Hz, 1H, Ar), 9.49 (br s, 1H, NH); 13C NMR (CDCl3) δ: 14.61, 24.85, 41.54, 48.44, 54.34, 55.85, 64.43, 111.37, 112.34, 115.04, 118.11, 120.21, 124.85, 129.17, 130.96, 136.01, 137.52, 148.54, 149.65, 167.38, 169.09, 169.40; Anal Calc'd. for C22H24NO7S: C, 57.38; H, 5.25; N, 6.08. Found: C, 57.31; H, 5.34; N, 5.83.

Provenance & Evidence

DOI10.6084/m9.figshare.5104873.v1
Patent numberUS07893101B2
Source datasetuspto-grants-2011_02
ORD IDord-516679e6b1b648e0a9f6f54eeabf2e0a
Source noteuspto-grants-2011_02