Reaction #802292

Reaction equation

HCl

1,4-dioxa-spiro[4.5]decane-8-carbonitrile

lithium bis(trimethylsilyl)amide

NaOH

iodomethane

→

title compound

Yield 85.0%

8-methyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Yield 85.0%

Solvents

THF

THF

Conditions

Workup

1. 1
   workup.STIRRINGstir at 0° C
2. 2
   workup.ADDITIONAdd satd
3. 3
   ExtractionNH4Cl, then brine, extract with EtOAc (2×)
4. 4
   Dryingdry the combined organics over MgSO4
5. 5
   Concentrationconcentrate to dryness
6. 6
   Otherto afford crude 8-methyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (1.33 g, 123%)
7. 7
   Temperaturecool to RT
8. 8
   Extractionextract with DCM (3×)
9. 9
   Dryingdry the combined organics over Na2SO4
10. 10
    Concentrationconcentrate to dryness

Procedure

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+).

Source