Bromomethylcyclopropane → 8-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

HRID 1865456Notes

Reaction equation

HRID 1865456 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]#[N:12])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.Br[CH2:14][CH:15]1[CH2:17][CH2:16]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH:15]1([CH2:14][C:8]2([C:11]#[N:12])[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)[CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 81503BromomethylcyclopropaneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 111164331,4-Dioxaspiro[4.5]decane-8-carbonitrile

Product 1

HCID 670726938-(Cyclopropylmethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1,4-dioxaspiro[4.5]decane-8-carbonitrile (20 g; 119.6136 mmol) and (bromomethyl)cyclopropane (17.76 g 12.6 ml; 131.57 mmol) in THF (100 ml) at −10° C. was added KHMDS (0.5M solution in toluene; 263.15 ml ; 131.57 mmol) dropwise and the solution allowed to warm to ambient temperature with stirring for 18 hours. The reaction was cooled in an ice bath and quenched with sat. ammonium chloride solution and the solvent evaporated. The residue was partitioned between EtOAc (300 ml) and water (100 ml adjusted to pH 4 with 1 N HCl). The organic phase was separated, dried over MgSO4, filtered and evaporated to give an orange oil. (21.0 g) 1H NMR δ (ppm)(CDCl3): 3.99-3.89 (4H, m), 2.08 (2H, d, J=13.5 Hz), 1.96-1.72 (9H, m), 0.96-0.82 (1H, m), 0.59-0.53 (2H, m), 0.17 (2H, q, J=5.1 Hz).

Workup

  1. temperatureThe reaction was cooled in an ice bath
  2. customquenched with sat. ammonium chloride solution
  3. customthe solvent evaporated
  4. customThe residue was partitioned between EtOAc (300 ml) and water (100 ml adjusted to pH 4 with 1 N HCl)
  5. customThe organic phase was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give an orange oil

Sources & evidence

ORD record
ord-05a39fda985b4432897ad1ac6c3b4ceb
Source dataset
uspto-grants-2009_12
Patent number
US07626056B2

Reaction notes

Loading…