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HuagongsheHuagongshe Chemistry Print Report · For research reference only
HRID 418546Generated: October 26, 2026

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

https://huagongshe.com/reaction/418546

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 numberUS08093283B2
Source datasetuspto-grants-2012_01
ORD IDord-3b865c7c0d2a42b9b200e22d5d129555
Source noteuspto-grants-2012_01