Benzoic acid, 4-fluoro-, ethyl ester → Ethyl 4-(3,3-dimethylpiperazin-1-yl)benzoate

HRID 16815Notes

Reaction equation

HRID 16815 reaction equation
F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH3:13][C:14]1([CH3:20])[CH2:19][NH:18][CH2:17][CH2:16][NH:15]1.C(N(C(C)C)C(C)C)C>CC(N(C)C)=O>[CH3:13][C:14]1([CH3:20])[NH:15][CH2:16][CH2:17][N:18]([C:2]2[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=2)[CH2:19]1

Participants

5

Reactant 3

HCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 81531DiisopropylethylamineHCID 146641862,2-Dimethylpiperazine

Product 1

HCID 57440420Ethyl 4-(3,3-dimethylpiperazin-1-yl)benzoateYield 55.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
200 °C

Procedure

Ethyl 4-fluorobenzoate (0.151 mL, 1 mmol), 2,2-dimethylpiperazine (0.137 g, 1.20 mmol) and N-ethyl-N-propan-2-ylpropan-2-amine (0.349 mL, 2.00 mmol) were dissolved in DMA (2 mL) and sealed into a microwave tube. The reaction was heated to 200° C. for 4 h in the microwave reactor and cooled to room temperature. The crude mixture was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 3.5M ammonia in methanol, fractions were evaporated to dryness to afford an oil. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 10% 2M ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 4-(3,3-dimethylpiperazin-1-yl)benzoate (0.145 g, 55.3%) as a white solid. 1H NMR (399.9 MHz, CDCl3) δ 1.15 (6H, d), 1.37 (3H, t), 2.38 (1H, d), 2.41 (1H, d), 2.96-3.04 (2H, m), 3.65-3.69 (2H, m), 4.33 (2H, q), 6.84-6.87 (2H, m), 7.89-7.93 (2H, m). MS: m/z 266 (MH+).

Workup

  1. customsealed into a microwave tube
  2. temperaturecooled to room temperature
  3. customThe crude mixture was purified by ion exchange chromatography
  4. washThe desired product was eluted from the column
  5. customwere evaporated to dryness
  6. customto afford an oil
  7. customThe crude product was purified by silica column chromatography
  8. washeluting with a gradient of 0 to 10% 2M ammonia/MeOH in DCM
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-a134039c6e424347960cbdea4ad5f687
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

Loading…