Cesium carbonate → Dimethyl 5-(4-benzylpiperazin-1-yl)isophthalate

HRID 14319Notes

Reaction equation

HRID 14319 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH2:16]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:16]([N:23]1[CH2:28][CH2:27][N:26]([C:2]2[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=2)[C:7]([O:9][CH3:10])=[O:8])[CH2:25][CH2:24]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 759941-BenzylpiperazineHCID 1039541,3-Benzenedicarboxylic acid, 5-bromo-, 1,3-dimethyl esterHCID 634876Binap, (A+-)-

Product 1

HCID 21086025Dimethyl 5-(4-benzylpiperazin-1-yl)isophthalateYield 65.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

In a sealed tube, a solution of dimethyl 5-bromoisophthalate (5.0 g, 18.3 mmol), N-benzylpiperazine (4.0 mL, 23.0 mmol), and cesium carbonate (8.4 g, 25.7 mmol) in toluene (36 mL) was degassed with nitrogen at room temperature for 20 minutes. Palladium (II) acetate (225 mg, 0.92 mmol) and BINAP (1.7 g, 2.74 mmol) were quickly added under nitrogen and the solution heated to 80° C. overnight to yield a yellow solution with a white suspension. The reaction mixture was cooled to room temperature, vacuum filtered, and the solid rinsed with fresh toluene. The filtrate was then concentrated under reduced pressure to yield a yellow oil. Purification by flash chromatography (silica, 80:20 hexanes/ethyl acetate) gave the desired dimethyl 5-(4-benzylpiperazin-1-yl)isophthalate (4.40 g): ESI MS m/z 369 [M+H]+.

Workup

  1. customto yield a yellow solution with a white suspension
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationvacuum filtered
  4. washthe solid rinsed with fresh toluene
  5. concentrationThe filtrate was then concentrated under reduced pressure
  6. customto yield a yellow oil
  7. customPurification by flash chromatography (silica, 80:20 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-3d20f470bf41421890f644c82639606d
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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