Nitrogen → HCID 58171476, compound

HRID 1752315Notes

Reaction equation

HRID 1752315 reaction equation
[C:1]([C:3](=[C:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[C:22]1([CH3:30])[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[Mg]Br.N#N>[Cu](I)I.C1COCC1>[C:1]([CH:3]([C:9]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[CH3:30])[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:13][CH2:14]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

6

Reactant 3

HCID 947NitrogenHCID 11551073TERT-BUTYL 4-(1-CYANO-2-ETHOXY-2-OXOETHYLIDENE)PIPERIDINE-1-CARBOXYLATEHCID 178424303HCID 178424303, compound

Product 1

HCID 58171476HCID 58171476, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate (196 mg, 0.667 mmol), copper iodide (39 mg, 0.3 equiv) and dry THF (4 mL) was degassed and recharged with N2 gas (3×), and cooled to 0° C. A solution of o-tolylmagnesium bromide (2.0 M in ether, 600 μL, 1.8 equiv) was added dropwise. The mixture was stirred 1 h at 0° C. under protection of N2 gas before being warmed to rt slowly and stirred 2 h at rt. LC-MS found the reaction was complete. The mixture was cooled to 0° C. again, quenched with 2% aq HCl to pH=˜5, extracted with EtOAc (3×35 mL). The combined organic layers were washed with satd NH4Cl (10 mL) and brine (10 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 12-g silica gel cartridge, eluted with a 0 to 30% EtOAc in hexanes gradient, to afford tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethyl)-4-o-tolylpiperidine-1-carboxylate (226 mg, 88%) as a clear oil.

Workup

  1. customwas degassed
  2. temperaturebefore being warmed to rt slowly
  3. temperatureThe mixture was cooled to 0° C. again
  4. customquenched with 2% aq HCl to pH=˜5
  5. extractionextracted with EtOAc (3×35 mL)
  6. washThe combined organic layers were washed with satd NH4Cl (10 mL) and brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration and concentration
  9. customthe residue was purified by chromatography on a 12-g silica gel cartridge
  10. washeluted with a 0 to 30% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-10335a9511654f67bfe9c87f7e676952
Source dataset
uspto-grants-2015_10
Patent number
US09163012B2

Reaction notes

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