Ethyl Acetate → 4-[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester

HRID 41701Notes

Reaction equation

HRID 41701 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:18]([O:22][C:23]([N:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[NH:28][CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].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:18]([O:22][C:23]([N:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:17][CH2:16][C:11]4([O:15][CH2:14][CH2:13][O:12]4)[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 121693418-(4-Bromophenyl)-1,4-dioxa-8-azaspiro[4.5]decaneHCID 16740533Tert-butyl 1,2,3,4-tetrahydroquinoxaline-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 668631744-[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl esterYield 58.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
150 °C

Procedure

0.31 g of 8-(4-bromophenyl)-1,4-dioxa-8-azaspiro[4.5]decane is placed in 5 ml of anhydrous o-xylene. 0.24 g of 3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester is added, then 0.15 g of sodium tert-butoxide is added, followed by 0.009 g of palladium acetate, and then the addition is completed with 0.0084 g of tri(tert-butyl)phosphine. The reaction mixture is heated at 150° C. for 4 h, then the heating is halted and the mixture is brought back to ambient temperature. Ethyl acetate is added and 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 heptane/ethyl acetate (4/1) solvent mixture. 0.27 g of 4-[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester is obtained.

Workup

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

Sources & evidence

ORD record
ord-a8f50c093ac846ea8b461c27c1bae8f6
Source dataset
uspto-grants-2013_09
Patent number
US08530657B2

Reaction notes

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