反应详情

温度

0 °C

Treat a 0° C. solution of 1,4-dioxa-spiro[4.5]decane-8-carbonitrile (1 g, 5.98 mmol) in THF (12 mL) drop-wise with lithium bis(trimethylsilyl)amide (1M, 6.88 mL, 6.88 mmol), stir at 0° C. for 1 h, add iodomethane (0.374 mL, 5.98 mmol) drop-wise and stir at 0° C. Add satd. NH4Cl, then brine, extract with EtOAc (2×), dry the combined organics over MgSO4 and concentrate to dryness to afford crude 8-methyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (1.33 g, 123%). Add THF (15 mL) and HCl (3M, 15 mL, 45 mmol), heat the mixture at 50° C. for 5 h, cool to RT, make basic with 3M NaOH, extract with DCM (3×), dry the combined organics over Na2SO4 and concentrate to dryness to afford the title compound (700 mg, 85%, 2 steps). 1H NMR (400 MHz, DMSO-d6): δ 2.48-2.41 (m, 2H), 2.30-2.23 (m, 2H), 2.19-2.12 (m, 2H), 1.84 (td, J=13.3, 4.5 Hz, 2H), 1.41 (s, 3H); MS(ESI) m/z: 138.1 (M+H+).

1. stirringstir at 0° C
2. additionAdd satd
3. extractionNH4Cl, then brine, extract with EtOAc (2×)
4. dry with materialdry the combined organics over MgSO4
5. concentrationconcentrate to dryness
6. customto afford crude 8-methyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (1.33 g, 123%)
7. temperaturecool to RT
8. extractionextract with DCM (3×)
9. dry with materialdry the combined organics over Na2SO4
10. concentrationconcentrate to dryness