Isopropyl iodide → HCID 67286778, compound

Participants

Reaction Conditions

Reaction Steps

(E)-3-{4-Oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (500 mg, 1.48 mmol, Intermediate 1, hydrochloride salt) was suspended in acetonitrile (65 ml). K2CO3 (818 mg, 5.92 mmol) and isopropyl iodide (523 mg, 3.07 mmol) were subsequently added and the mixture was heated at 75° C. for 14 h. The solvent was evaporated and the residue was diluted with water and extracted with ethyl acetate. The combined organic phases were dried, evaporated, and the crude oily residue (575 mg) was hydrolyzed as described in Example 55, Step B, giving (E)-3-{1′-isopropyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (475 mg) as an orange solid (hydrochloride salt). The resulting acid was suspended in DCM (16 ml), TEA (0.30 ml) was added, and the resulting clear solution was treated with NH2OTHP following the procedure described in Example 1, Step B, giving (E)-3-{1′-isopropyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide as an orange solid (314 mg). The compound was dissolved in DCM (4 ml) and treated with 1 M HCl in diethyl ether (6 ml, 6 mmol) as described in Example 2, Step D, giving a light pink solid (192 mg, trifluoroacetate salt) after purification by preparative HPLC.

Provenance & Evidence