Ethyl Acetate → 4-{4-[4-(pyridin-4-yloxy)piperidin-1-yl]phenyl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester

HRID 1510046Notes

Reaction equation

HRID 1510046 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:21]([O:25][C:26]([N:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].CC(C)([O-])C.[Na+].C(OCC)(=O)C>CC1C=CC=CC=1C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[C:21]([O:25][C:26]([N:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][CH:11]([O:14][C:15]4[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=4)[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 16740533Tert-butyl 1,2,3,4-tetrahydroquinoxaline-1-carboxylateHCID 23676156Sodium t-butoxideHCID 668633164-[1-(4-Bromophenyl)piperidin-4-yloxy]pyridine

Product 1

HCID 668633364-{4-[4-(pyridin-4-yloxy)piperidin-1-yl]phenyl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl esterYield 62.8%

Reagents, catalysts & solvents 3

HCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
150 °C

Procedure

1.2 g of 4-[1-(4-bromophenyl)piperidin-4-yloxy]pyridine are placed in 20 ml of anhydrous o-xylene. 0.844 g of 3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester is added, then 0.519 g of sodium tert-butoxide is added, followed by 0.032 g of palladium acetate, and then addition is completed with 0.029 g of tri(tert-butyl)phosphine. The reaction mixture is heated at 150° C. for 6 h. Heating is subsequently halted, the mixture is brought back to ambient temperature and ethyl acetate is added. The mixture is washed twice with water and then twice with a saturated aqueous sodium chloride solution. The organic phase is dried over sodium sulphate and concentrated under reduced pressure. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of a dichloromethane/methanol (99/1 to 97/3) mixture. 1.1 g of 4-{4-[4-(pyridin-4-yloxy)piperidin-1-yl]phenyl}-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester are obtained.

Workup

  1. additionaddition
  2. temperatureHeating
  3. customis brought back to ambient temperature
  4. washThe mixture is washed twice with water
  5. dry with materialThe organic phase is dried over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product obtained
  8. customis chromatographed on silica gel, elution

Sources & evidence

ORD record
ord-e4e5b2d0aa3141bbbc8f032b85706553
Source dataset
uspto-grants-2012_07
Patent number
US08211892B2

Reaction notes

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