Hydrochloric Acid → Ethyl 8-(cyanomethyl)-1,4-dioxaspiro[4.5]decane-8-carboxylate

HRID 2092672Notes

Reaction equation

HRID 2092672 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:15][CH2:14][C:9]2([O:13][CH2:12][CH2:11][O:10]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH:16]([N-:19]C(C)C)(C)[CH3:17].[Li+].BrCC#N.Cl>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1([CH2:17][C:16]#[N:19])[CH2:15][CH2:14][C:9]2([O:10][CH2:11][CH2:12][O:13]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11534BromoacetonitrileHCID 2724682Lithium diisopropylamideHCID 10488810Ethyl 1,4-dioxaspiro(4.5)decane-8-carboxylate

Product 1

HCID 58230182Ethyl 8-(cyanomethyl)-1,4-dioxaspiro[4.5]decane-8-carboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-5 °C

Procedure

A solution of 1,4-dioxa-spiro[4.5]decane-8-carboxylic acid ethyl ester (1.0 g, obtained in example 133, step 1) in THF (8 mL) was added dropwise over a period of 10 minutes to a solution of lithiumdiisopropylamide (2M in THF/heptane/ethyl benzene, 4.67 mL) in THF (12 mL) kept at −5° C. (ice/methanol bath). Stirring was continued for 1 hour at 0° C. The reaction mixture was re-cooled to −5° C. and a solution of bromoacetonitrile (0.65 mL, [CAS Reg. No. 590-17-0]) in THF (4 mL) was added dropwise over a period of 10 minutes. Stirring was then continued for 16 hours at RT. The reaction mixture was poured into ice/water and was acidified with 1M aqueous HCl solution (50 mL). The aqueous layer was extracted two times with ethyl acetate and the combined organic layers were washed with brine, dried over Na2SO4 and filtered. The solvent was evaporated and the residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a brown liquid (528 mg, 45%). MS (m/e): 254.2 [MH+].

Workup

  1. customkept at −5° C.
  2. stirringStirring
  3. waitwas then continued for 16 hours at RT
  4. extractionThe aqueous layer was extracted two times with ethyl acetate
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customThe solvent was evaporated
  9. customthe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-541a83edf18d4daa8b008d6e36586194
Source dataset
uspto-grants-2013_05
Patent number
US08440710B2

Reaction notes

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