Hydrochloric Acid → Benzyl 3-(2-cyanoacetyl)-pyrrolidine-1-carboxylate
Reaction equation
[C:1](#[N:3])[CH3:2].C([Li])CCC.C[O:10][C:11]([CH:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:14]1)=O.Cl>O1CCCC1.O>[C:1]([CH2:2][C:11]([CH:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:14]1)=[O:10])#[N:3]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -78 °C
Procedure
To a solution of acetonitrile (708 μL, 13.5 mmol) in tetrahydrofuran (30 mL) was added n-butyl lithium (1.6 M solution in hexane, 7.75 mL, 12.4 mmol) at −78° C. The solution was stirred at −78° C. for 10 minutes and a solution of EXAMPLE 24A (3.0 g, 11.34 mmol) in 10 mL of tetrahydrofuran was added. The mixture was stirred at −78° C. for 1 hour and was warmed up to −20° C. over 3 hours. Water was added and the mixture acidified to pH 3 with 2N hydrochloric acid. The mixture was partitioned between ethyl acetate and brine and the organic phase concentrated. The residue was purified by flash chromatography on silica gel using 30-80% ethyl acetate in hexane to give the title compound (1.91 g, 61%). MS(DCI): m/z 273 (M+1)+.
Workup
- stirringThe mixture was stirred at −78° C. for 1 hour
- temperaturewas warmed up to −20° C. over 3 hours
- customThe mixture was partitioned between ethyl acetate and brine
- concentrationthe organic phase concentrated
- customThe residue was purified by flash chromatography on silica gel using 30-80% ethyl acetate in hexane
Sources & evidence
- ORD record
- ord-48c94bab5cb94b68a427b95a92611455
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08546368B2
Reaction notes
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