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HuagongsheHuagongshe Chemistry Print Report · For research reference only
HRID 1062678Generated: November 3, 2026

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

https://huagongshe.com/reaction/1062678

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) δ1.47 (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, CHH), 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) δ14.61, 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 numberUS06962940B2
Source datasetuspto-grants-2005_11
ORD IDord-b3c88df96a1a4ce49071b5714796f36c
Source noteuspto-grants-2005_11