Hydrochloric Acid → 1-Cyanomethyl-cyclohexanecarboxylic acid methyl ester
Reaction equation
[CH:1]1([C:7]([O:9][CH3:10])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:11]([N-:14]C(C)C)(C)[CH3:12].[Li+].CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.BrCC#N.Cl>C1COCC1.C(OCC)(=O)C>[CH3:10][O:9][C:7]([C:1]1([CH2:12][C:11]#[N:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:8]Participants
8
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -78 °C
Procedure
Treat a −78° C. solution of methyl cyclohexane carboxylate (15.0 g, 0.105 mol) in THF (150 mL) with a 2M solution of lithium diisopropylamide in heptane/THF/ethylbenzene (63.3 mL, 0.126 mol) and stir at −78° C. for 20 minutes under N2. Treat the reaction with bromoacetonitrile (25.31 g, 0.211 mol) and stir at −78° C. for 15 minutes. Warm the reaction to room temperature and stir 4 hours. Acidify the reaction with 1 N HCl and then dilute the reaction with ethyl acetate and wash with water. Dry the organic layer (Na2SO4) and remove the solvent in vacuo to afford crude product. Purify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel to afford 7.78 g (41%) of the titled product. Rf=0.32 (3/1 hexanes/ethyl acetate).
Workup
- additionTreat
- stirringstir at −78° C. for 15 minutes
- temperatureWarm
- customthe reaction to room temperature
- stirringstir 4 hours
- additiondilute
- washwash with water
- dry with materialDry the organic layer (Na2SO4)
- customremove the solvent in vacuo
- customto afford crude product
- customPurify with a 0 to 30% ethyl acetate in hexanes gradient on silica gel
Sources & evidence
- ORD record
- ord-fa5e979fc0fc468c9726504a37d7b17b
- Source dataset
- uspto-grants-2011_06
- Patent number
- US07968585B2
Reaction notes
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