Ethyl Acetoacetate → [4-(4-Methyl-piperazine-1-sulfonyl)phenyl]acetic acid ethyl ester

HRID 1712983Notes

Reaction equation

HRID 1712983 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:18]([O:24][CH2:25][CH3:26])(=[O:23])[CH2:19]C(C)=O.C(P(C(C)(C)C)C1(C)CC=CC=C1C1C=CC=CC=1)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH2:25]([O:24][C:18](=[O:23])[CH2:19][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1)[CH3:26]

Participants

8

Reactant 4

HCID 8868Ethyl AcetoacetateHCID 62657Potassium Phosphate, TribasicHCID 7107291-(4-Bromophenylsulfonyl)-4-methylpiperazineHCID 674862892-(Di-tert-butylphosphino)-2-methyl biphenyl

Product 1

HCID 44473999[4-(4-Methyl-piperazine-1-sulfonyl)phenyl]acetic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

The title A compound, 1-(4-bromo-benzenesulfonyl)-4-methyl-piperazine (5.00 g, 15.663 mmol), ethyl acetoacetate (2.97 mL, 23.495 mmol), 2-(di-tert-butylphosphino)-2-methyl biphenyl (98 mg, 0.313 mmol), palladium acetate (105 mg, 0.157 mmol) and potassium phosphate (9.97 g, 46.989 mmol) are charged to a flask. Toluene (60 mL) is added. The reaction is heated at 90° C. overnight, then cooled to RT. The reaction mixture is poured onto ethyl acetate and water. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated to afford a brown oil. This is chromatographed using 0→20% methanol in ethyl acetate to afford [4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-acetic acid ethyl ester as a tan solid which contains ˜8% of the acylated material: LC/MS 327.1 (M+1); 1H NMR (400 MHz, DMSO-D6) δ 1.2 (t, J=7.1 Hz, 3 H) 2.1 (s, 3 H) 2.3 (m, 4 H) 2.9 (d, J=4.3 Hz, 4 H) 3.8 (s, 2 H) 4.1 (q, J=7.1 Hz, 2 H) 7.5 (d, J=8.3 Hz, 2 H) 7.6 (d, 7.7 (m, 2 H). C. 3-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic Acid Ethyl ester

Workup

  1. temperaturecooled to RT
  2. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford a brown oil
  6. customThis is chromatographed

Sources & evidence

ORD record
ord-4f5261953e0d40ec8ee900ff50fbb5ad
Source dataset
uspto-grants-2010_09
Patent number
US07795257B2

Reaction notes

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