tert-Butyl cyanoacetate → HCID 22258721, compound

HRID 412271Notes

Reaction equation

HRID 412271 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:10]=1[C:23](=O)[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:26]([CH:28]1[CH2:33][CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29]1)=O.[C:41]([O:45][C:46](=[O:50])[CH2:47][C:48]#[N:49])([CH3:44])([CH3:43])[CH3:42].C([O-])(=O)C.[NH4+:55]>COCCOC>[NH2:49][C:48]1[N:55]=[C:23]([C:10]2[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:14][CH:13]=[CH:12][C:11]=2[O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:24]=[C:26]([CH:28]2[CH2:33][CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29]2)[C:47]=1[C:46]([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:50]

Participants

6

Reactant 4

HCID 70693tert-Butyl cyanoacetateHCID 517165Ammonium AcetateHCID 8388661-[2,6-bis(benzyloxy)phenyl]ethanone2×HCID 99644481-Boc-piperidine-3-carboxaldehyde2×

Product 1

HCID 22258721HCID 22258721, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-[2,6-bis(benzyloxy)phenyl]ethanone (8.00 g, 24.067 mmol) (starting compound 1E), tert-butyl 3-formyl-1-piperidinecarboxylate (5.133 g, 24.067 mmol) (starting compound 2B), tert-butylcyanoacetate (3.398 g, 24.067 mmol), and ammonium acetate (5.432 g, 72.202 mmol) in 1,2-dimethoxyethane (24 mL) was stirred at 100° C. in a sealed tube overnight. After cooled to room temperature, the reaction mixture was partitioned between ethyl acetate and water. The separated organic phase was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was diluted with 30 mL of dichloromethane, and MnO2 was added to the mixture, and then the mixture was stirred at room temperature for 5 hrs. The mixture was filtered on Celite®, and concentrated under reduced pressure. The resulting residue (liquid) was purified by column chromatography on silica gel (hexane/ethyl acetate=2/1) to give tert-butyl 2-amino-6-[2,6-bis(benzyloxy)phenyl]-4-[1-(tert-butoxycarbonyl)-3-piperidinyl]nicotinate as a pale yellow oil. (2.5 g, yield; 16%)

Workup

  1. temperatureAfter cooled to room temperature
  2. customthe reaction mixture was partitioned between ethyl acetate and water
  3. washThe separated organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was diluted with 30 mL of dichloromethane, and MnO2
  8. additionwas added to the mixture
  9. stirringthe mixture was stirred at room temperature for 5 hrs
  10. filtrationThe mixture was filtered on Celite®
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting residue (liquid) was purified by column chromatography on silica gel (hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-5d0358076ba54454b05dc5c59bd36d26
Source dataset
uspto-grants-2003_05
Patent number
US06562811B1

Reaction notes

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