Hydrochloric Acid → 4-Acetyl-6-chloro-3-ethoxy-2-(2-oxo-1,3-oxazolidin-5-yl)benzonitrile

HRID 1499937Notes

Reaction equation

[C:1]([C:4]1[C:5]([O:24][CH2:25][CH3:26])=[C:6]([CH:13]([OH:23])[CH2:14][NH:15][C:16](=O)[O:17]C(C)(C)C)[C:7]([C:11]#[N:12])=[C:8]([Cl:10])[CH:9]=1)(=[O:3])[CH3:2].Cl.C(N(CC)C(C)C)(C)C.C1N=CN(C(N2C=NC=C2)=O)C=1>O1CCOCC1>[C:1]([C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([C:11]#[N:12])=[C:6]([CH:13]2[O:23][C:16](=[O:17])[NH:15][CH2:14]2)[C:5]=1[O:24][CH2:25][CH3:26])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

tert-Butyl [2-(3-acetyl-5-chloro-6-cyano-2-ethoxyphenyl)-2-hydroxyethyl]carbamate (290 mg, 0.76 mmol) (racemic mixture from step 2) was treated with 4.0 M hydrogen chloride in 1,4-dioxane (6.1 mL) for 15 minutes and the mixture was evaporated. The residue was dissolved in tetrahydrofuran (2.3 mL) and N,N-diisopropylethylamine (0.66 mL, 3.8 mmol). N,N-carbonyldiimidazole (250 mg, 1.5 mmol) was added and the reaction mixture was refluxed at 70° C. overnight. The reaction mixture was evaporated. Purification on silica gel using ethyl acetate in hexane (0-100%) gave the desired compound as a racemic mixture, 110 mg, 47%. LCMS calculated for C14H14ClN2O4(M+H)+: m/z=309.1; found: 309.1. 1H NMR (400 MHz, DMSO-d6): δ 8.00 (br s, 1 H), 7.93 (s, 1 H), 5.99 (m, 1 H), 3.89 (m, 1 H), 3.81 (m, 2 H), 3.52 (m, 1 H), 2.58 (s, 3 H), 1.23 (m, 3 H).

Workup

customthe mixture was evaporated
dissolutionThe residue was dissolved in tetrahydrofuran (2.3 mL)
customThe reaction mixture was evaporated
customPurification on silica gel

Sources & evidence

ORD record: ord-d69a7467905c4bd1890af0a408b9b7ab
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199982B2

Reaction notes

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