Tris(1,1-dimethylethyl)phosphine → 4-[4-(4-(Benzyloxycarbonyl)piperazin-1-yl)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester

HRID 41694Notes

Reaction equation

HRID 41694 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:24]([O:28][C:29]([N:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[NH:34][CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1C=CC=CC=1C>[C:24]([O:28][C:29]([N:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[N:34]([C:20]2[CH:21]=[CH:22][C:17]([N:14]3[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:10])[CH2:12][CH2:13]3)=[CH:18][CH:19]=2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 16740533Tert-butyl 1,2,3,4-tetrahydroquinoxaline-1-carboxylateHCID 23676156Sodium t-butoxideHCID 46739494Benzyl 4-(4-bromophenyl)piperazine-1-carboxylate

Product 1

HCID 668635804-[4-(4-(Benzyloxycarbonyl)piperazin-1-yl)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl esterYield 78.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
150 °C

Procedure

8.43 g of 4-(4-bromophenyl)piperazine-1-carboxylic acid benzyl ester are placed in a 500 ml three-necked flask under a nitrogen atmosphere. 170 ml of anhydrous o-xylene, 5.01 g of 3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester and then 3.08 g of sodium tert-butoxide are added, followed by 0.48 g of palladium acetate, and then the addition is completed with 0.53 ml of tri(tert-butyl)phosphine. The reaction mixture is heated at 150° C. for 18 h. Heating is halted and the mixture is brought back to ambient temperature. The o-xylene is evaporated and the mixture is taken up in ethyl acetate before filtering it through celite. The organic phase is washed with water and then with a saturated aqueous sodium chloride solution. The aqueous phase is extracted with ethyl acetate. The organic phases are combined and then dried over sodium sulphate, filtered through a sintered glass filter and concentrated under vacuum. 8.9 g of 4-[4-(4-(Benzyloxycarbonyl)piperazin-1-yl)phenyl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester are obtained after purification on a silica column, elution being carried out with a gradient of heptane/ethyl acetate solvent varying from 95/5 to 60/40).

Workup

  1. additionthe addition
  2. temperatureHeating
  3. customis brought back to ambient temperature
  4. customThe o-xylene is evaporated
  5. filtrationbefore filtering it through celite
  6. washThe organic phase is washed with water
  7. extractionThe aqueous phase is extracted with ethyl acetate
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered through a sintered glass
  10. filtrationfilter
  11. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-cdb735c016a343f5824de698de62cdc0
Source dataset
uspto-grants-2013_09
Patent number
US08530657B2

Reaction notes

Loading…