3-Hydroxy-4-nitrobenzaldehyde → Tert-butyl 2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-4-(3-hydroxy-4-nitrophenyl)nicotinate

HRID 2218263Notes

Reaction equation

HRID 2218263 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.[OH:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[N+:34]([O-:36])=[O:35])[CH:29]=O.[C:37]([CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])#[N:38].C([O-])(=O)C.[NH4+:51]>COCCOC>[NH2:38][C:37]1[N:51]=[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:29]([C:28]2[CH:31]=[CH:32][C:33]([N+:34]([O-:36])=[O:35])=[C:26]([OH:25])[CH:27]=2)[C:39]=1[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41]

Participants

6

Reactant 4

HCID 697123-Hydroxy-4-nitrobenzaldehydeHCID 70693tert-Butyl cyanoacetateHCID 517165Ammonium AcetateHCID 99233791-(2-(Cyclopropylmethoxy)-6-(4-methoxybenzyloxy)phenyl)ethanone

Product 1

HCID 69145610Tert-butyl 2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-4-(3-hydroxy-4-nitrophenyl)nicotinate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}ethanone (starting compound 1-A′ 2.00 g, 6.13 mmol), 3-hydroxy-4-nitrobenzaldehyde (2.05 g, 12.26 mmol), tert-butyl cyanoacetate (1.73 g, 12.26 mmol), ammonium acetate (1.42 g, 18.38 mmol) and 1,2-dimethoxyethane (2.0 mL) was placed in a sealed tube and was stirred at 100° C. for 8 hrs. After being cooled to room temperature, the mixture was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and water. The separated organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (hexane:ethyl acetate, 1:1) to give tert-butyl 2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-4-(3-hydroxy-4-nitrophenyl)nicotinate. (2.32 g, 62%); LC-MS (m/z=614, M+1)

Workup

  1. customwas placed in a sealed tube
  2. temperatureAfter being cooled to room temperature
  3. concentrationthe mixture was concentrated under reduced pressure
  4. customthe residue was partitioned between ethyl acetate and water
  5. washThe separated organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-2e4ac5d30cb24481a0ebb8081505c807
Source dataset
uspto-grants-2008_08
Patent number
US07410986B2

Reaction notes

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