Cesium carbonate → (R)-4-(4-benzyloxyphenyl)-2-methylpiperazine-1-carboxylic acid benzyl ester

HRID 2172235Notes

Reaction equation

HRID 2172235 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][CH2:13][C@H:12]1[CH3:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29](Br)=[CH:28][CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:27][CH:28]=2)[CH2:13][C@H:12]1[CH3:17])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 1388351-Bromo-4-phenylmethoxybenzeneHCID 40424346(R)-benzyl 2-methylpiperazine-1-carboxylateHCID 44558591Tri-t-butylphosphine fluoroborate

Product 1

HCID 70873580(R)-4-(4-benzyloxyphenyl)-2-methylpiperazine-1-carboxylic acid benzyl esterYield 79%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

(R)-2-Methylpiperazine-1-carboxylic acid benzyl ester (4.42 g, 18.9 mmol), 1-benzyloxy-4-bromobenzene (5.95 g, 22.6 mmol), cesium carbonate (8.60 g, 26.4 mmol) and toluene (49 ml) were mixed, and the atmosphere was replaced with nitrogen. Palladium acetate (0.42 g, 1.9 mmol) and tri-tert-butylphosphine tetrafluoroborate (0.66 g, 2.3 mmol) were added thereto and stirred at 90 to 100° C. for 2 days. Water and ethyl acetate were added to the reaction mixture, the mixture was filtered through Celite to remove insoluble matter. The filtrate was separated into layers. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→70:30) to afford the title compound as a brown oil (6.18 g, 79%).

Workup

  1. filtrationthe mixture was filtered through Celite
  2. customto remove insoluble matter
  3. customThe filtrate was separated into layers
  4. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→70:30)

Sources & evidence

ORD record
ord-a1f16b1433cc4bb28ba66ed5e97417c0
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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