Trifluoroacetic acid → ethyl 1-Cyanomethyliso-nipecotate
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH2:19][C:20]#[N:21])[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7]1)=[O:5])[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1([CH2:19][C:20]#[N:21])[CH2:7][CH2:8][NH:9][CH2:10][CH2:11]1)=[O:5])[CH3:2]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
4-Cyanomethyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (36 g) was dissolved in methylene chloride (600 ml), cooled to 0° C. then trifluoroacetic acid (207.8 g, 134.9 ml) was added under an argon atmosphere and the mixture was stirred over night allowing the temperature of the reaction mixture to rise to RT. The reaction mixture was then concentrated in vacuo, the residue taken up in methylene chloride and washed several times with 1M aqueous NaOH (to pH 12). The layers were separated, the organic layer washed with brine, dried over sodium sulphate and concentrated to give 4-cyanomethyl-piperidine-4-carboxylic acid ethyl ester a brown oil (14.2 g) which was essentially pure according to NMR and used in next reaction step without further purification. MS (ESI): 197.2 (MH+).
Workup
- customto rise to RT
- concentrationThe reaction mixture was then concentrated in vacuo
- washwashed several times with 1M aqueous NaOH (to pH 12)
- customThe layers were separated
- washthe organic layer washed with brine
- dry with materialdried over sodium sulphate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-2eaf1f89899f43118834db5b92f9f68a
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08329904B2
Reaction notes
Loading…