Ethylene Glycol → HCID 86591408, compound

Participants

Reaction Steps

4-[(3-oxo-1-pyrrolidinyl)sulfonyl]benzonitrile 23b (11.6 g, 46.3 mmol) was suspended in toluene (110 ml) and stirred at room temp. Ethylene glycol (6.2 ml, 6.9 g, 111 mmol) and para-toluene sulphonic acid monohydrate (100 mg, 0.53 mmol) were added. The reaction mixture was heated to reflux under Dean-Stark conditions and monitored by water collection and TLC (5% methanol in DCM). If necessary for the completion of the reaction (typically within 3 h), further portions of p-TSA were added. When complete the reaction mixture was washed with saturated sodium bicarbonate solution (55 ml) and water (2×55 ml). The organic layer was filtered through cotton wool and then concentrated in vacuo to approximately 50 ml or until precipitation started. Hexane (150 ml) was added and the suspension stirred at 0-5° C. for 10-20 min, filtered and washed with hexane (2×50 ml). The residue was air dried to yield 13.0 g (96%) ketal 4-(1,4-dioxa-7-azaspiro[4.4]non-7-ylsulfonyl)benzonitrile 23c. 4-(1,4-dioxa-7-azaspiro[4.4]non-7-ylsulfonyl)benzonitrile 23c was progressed according to the procedure described for example 7b which finally leads to 4-chloro-N-(4-{[3-({2-[3-(trifluoromethyl)phenyl]ethyl}amino)-1-pyrrolidinyl]sulfonyl}benzyl)benzamide 23. M/Z APCI 566.0 (M+1), 564.2 (M−1), 1H-NMR (DMSO-d6) δ9.57 (m, 2H, H—N15), 9.42 (t, 1H, H—N5, 3J=5.92 Hz), 7.99 (d, 2H, 3J=8.65 Hz, H—C2, 3), 7.82 (d, 2H, H—C8, 9), 7.71-7.59 (m, 8H, H—C1,4,7,10,18,19,20,21), 4.62 (d, 2H, 3J=5.92 Hz, H—C6), 3.75 (m, 1H, H—C12), 3.53-3.33 (m, 2H under DMSO-H2O signal, H—C16), 3.27-3.03 (m, 6H, H—C11, 14, 17), 2.17 (m, 1H, Ha—C13), 2.04 (m, 1H, Hb—C13).

Provenance & Evidence