tert-Butyl cyanoacetate → Tert-butyl 2-amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-{2-[(4-methoxybenzyl)oxy]phenyl}nicotinate

HRID 1767351Notes

Reaction equation

HRID 1767351 reaction equation
[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15](=O)[CH3:16])=[CH:5][CH:4]=1.[CH:20]([CH:22]1[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[CH2:23]1)=O.[C:38]([CH2:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])#[N:39].C([O-])(=O)C.[NH4+:52]>COCCOC>[NH2:39][C:38]1[N:52]=[C:15]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:7][C:6]2[CH:18]=[CH:19][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH:16]=[C:20]([CH:22]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])[CH2:23]2)[C:40]=1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]

Participants

6

Reactant 4

HCID 70693tert-Butyl cyanoacetateHCID 517165Ammonium AcetateHCID 9899653Benzyl 3-formylpiperidine-1-carboxylate2×HCID 98998251-{2-[(4-Methoxybenzyl)oxy]phenyl}ethanone2×

Product 1

HCID 10232833Tert-butyl 2-amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-{2-[(4-methoxybenzyl)oxy]phenyl}nicotinateYield 14.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 1-{2-[(4-methoxybenzyl)oxy]phenyl}ethanone (14.2 g, 55.4 mmol) (starting compound 1D), benzyl 3-formyl-1-piperidinecarboxylate (13.7 g, 55.4 mmol) (starting compound 2C), tert-butyl cyanoacetate (7.8 g, 55.4 mmol), and ammonium acetate (9.8 g, 166.1 mmol) in 1,2-dimethoxyethane (60 mL) was stirred under reflux for 3.5 hrs. After cooled to room temperature, the mixture was partitioned between ethyl acetate and water. The separated organic phase was washed with water and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane, 1:2) to give tert-butyl 2-amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-{2-[(4-methoxybenzyl)oxy]phenyl}nicotinate as a pale yellow oil (4.89 g, yield; 14%).

Workup

  1. temperatureunder reflux for 3.5 hrs
  2. customthe mixture was partitioned between ethyl acetate and water
  3. washThe separated organic phase was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (ethyl acetate:hexane, 1:2)

Sources & evidence

ORD record
ord-6940be507e3649c88866e36416c503df
Source dataset
uspto-grants-2007_06
Patent number
US07232909B2

Reaction notes

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