Chloranil → HCID 10122432, compound

HRID 2223165Notes

Reaction equation

HRID 2223165 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:7]=2[C:22](=O)[CH3:23])[CH2:3][CH2:2]1.[CH:25]([CH:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]1)=O.[C:40]([O:44][C:45](=[O:49])[CH2:46][C:47]#[N:48])([CH3:43])([CH3:42])[CH3:41].C([O-])(=O)C.[NH4+:54].C1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C=1Cl.O=C1O[C@H]([C@H](CO)O)C(O)=C1O>O1CCOCC1.C(OCC)(=O)C>[NH2:48][C:47]1[N:54]=[C:22]([C:7]2[C:8]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][CH2:4][CH:1]2[CH2:3][CH2:2]2)[CH:23]=[C:25]([CH:27]2[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]2)[C:46]=1[C:45]([O:44][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:49]

Participants

9

Reactant 6

HCID 8371ChloranilHCID 70693tert-Butyl cyanoacetateHCID 517165Ammonium AcetateHCID 99233791-(2-(Cyclopropylmethoxy)-6-(4-methoxybenzyloxy)phenyl)ethanoneHCID 99644481-Boc-piperidine-3-carboxaldehydeHCID 54670067L-Ascorbic Acid

Product 1

HCID 10122432HCID 10122432, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}ethanone (10.00 g, 30.638 mmol), tert-butyl 3-formyl-1-piperidinecarboxylate (13.069 g, 61.275 mmol), tert-butylcyanoacetate (8.650 g, 61.275 mmol), and ammonium acetate (6.902 g, 91.913 mmol) in dioxane (10 mL) was stirred at 90° C. overnight. After cooled to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL). To the mixture was added chloranil (1.507 g, 6.128 mmol), and stirred at room temperature. After 1.5 hrs, ascorbic acid (1.079 g, 6.128 mmol) was added to the mixture. After stirred for 1.5 hrs, the mixture was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over MgSO4, filtered, and then concentrated under reduced pressure. The resulting residue was purified by column chromatography on Silica-gel (hexane/ethyl acetate=2/1) to give tert-butyl 2-amino-4-[1-(tert-butoxycarbonyl)-3-piperidinyl]-6-{2-(cyclopropyl-methoxy)-6-[(4-methoxybenzyl)oxy]phenyl}nicotinate as a pale brown form (4.9 g, 24%).

Workup

  1. temperatureAfter cooled to room temperature
  2. stirringstirred at room temperature
  3. waitAfter 1.5 hrs
  4. stirringAfter stirred for 1.5 hrs
  5. customthe mixture was partitioned between ethyl acetate and water
  6. washThe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by column chromatography on Silica-gel (hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-5af8908782c4416b99623b5301be832f
Source dataset
uspto-grants-2008_05
Patent number
US07375103B2

Reaction notes

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