Sodium hydride → tert-Butyl 4-cyano-4-(pyridin-3-yl)piperidine-1-carboxylate
Reaction equation
[H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][C:10]#[N:11])[CH:4]=1.Cl[CH2:13][CH2:14][N:15]([CH2:23][CH2:24]Cl)[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19]>CN(C)C=O>[C:10]([C:9]1([C:5]2[CH:4]=[N:3][CH:8]=[CH:7][CH:6]=2)[CH2:24][CH2:23][N:15]([C:16]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:22])[CH2:14][CH2:13]1)#[N:11]Participants
Conditions
- Temperature
- 0 °C
Procedure
A flask was charged with sodium hydride (5.08 g, 127 mmol) and dimethylformamide (100 ml) at 0° C. under nitrogen. 2-(Pyridin-3-yl)acetonitrile (5 g, 42.3 mmol) was added in 25 mL of dimethylformamide via addition funnel over 20 min. After 20 min, tert-butyl bis(2-chloroethyl)carbamate (12.81 g, 52.9 mmol) was added in 20 mL of dimethylformamide via addition funnel over 20 min. The reaction was allowed to stir at 0° C. for 2 h and then at 60° C. for 12 h. The reaction was quenched with 10% sodium bicarbonate (100 mL) and extracted with ethyl acetate (5×100 mL). The organics were collected, washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified via column chromatography (10% 2M ammonia in methanol, 90% dichloromethane) to yield 7.5 g (49%) of desired product. Mass Spec.: 288.20 (MH)+. LC tr=1.380 min (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=2 min, Flow rate=4 mL/min)
Workup
- waitat 60° C. for 12 h
- customThe reaction was quenched with 10% sodium bicarbonate (100 mL)
- extractionextracted with ethyl acetate (5×100 mL)
- customThe organics were collected
- washwashed with brine
- dry with materialdried over sodium sulfate
- concentrationconcentrated in vacuo
- customThe residue was purified via column chromatography (10% 2M ammonia in methanol, 90% dichloromethane)
Sources & evidence
- ORD record
- ord-b48585cb2810475f85a2c92a4425e660
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08383821B2
Reaction notes
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