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

HRID 2092665Notes

Reaction equation

HRID 2092665 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
0 °C

Procedure

A solution of 1,4-dioxa-spiro[4.5]decane-8-carboxylic acid ethyl ester (1.0 g, obtained in example 121, step 1) in THF (8 mL) was added dropwise over a period of 10 minutes at −5° C. (ice/methanol bath) to a solution of lithiumdiisopropylamide (2M in THF/heptane/ethyl benzene, 4.67 mL) in THF (12 mL) and the mixture was stirred 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. The mixture was allowed to warm to RT and stirring was continued for 16 hours. The reaction 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. temperatureThe reaction mixture was re-cooled to −5° C.
  2. temperatureto warm to RT
  3. stirringstirring
  4. waitwas continued for 16 hours
  5. extractionThe aqueous layer was extracted two times with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe solvent was evaporated
  10. customthe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-55016b567aa34ac4b09c412ae9a24afc
Source dataset
uspto-grants-2013_05
Patent number
US08440710B2

Reaction notes

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