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HuagongsheHuagongshe Chemistry Print Report · For research reference only
HRID 1442848Generated: October 31, 2026

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

https://huagongshe.com/reaction/1442848

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 numberUS07659302B2
Source datasetuspto-grants-2010_02
ORD IDord-9350b915265a429c925b8b9df0871cf8
Source noteuspto-grants-2010_02