Hydrochloric Acid → alpha-[[(2,4,6-Trimethoxyphenyl)amino]carbonyl] benzene acetic acid ethyl ester

HRID 1756978Notes

Reaction equation

HRID 1756978 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]1([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:25][O:26][C:27]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=1[N:37]=[C:38]=[O:39].Cl>C1COCC1>[CH2:23]([O:22][C:20](=[O:21])[CH:19]([C:38]([NH:37][C:28]1[C:29]([O:35][CH3:36])=[CH:30][C:31]([O:33][CH3:34])=[CH:32][C:27]=1[O:26][CH3:25])=[O:39])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:24]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7590Ethyl phenylacetateHCID 7912DiisopropylamineHCID 100818122,4,6-Trimethoxyphenyl isocyanateHCID 178418339Butyllithium

Product 1

HCID 10690735alpha-[[(2,4,6-Trimethoxyphenyl)amino]carbonyl] benzene acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred, room temperature solution of diisopropylamine (43.4 mL, 0.310 mol) in dry THF (1.2 L) was added a 2.5M solution (124 mL, 0.31 mol) of n-butyl lithium in hexanes in one portion, and the mixture was cooled to -78° C. To the solution was added under nitrogen a solution of phenylacetic acid, ethyl ester (50.8 g, 0.309 mol) in THF (500 mL) over 15 minutes. Stirred 2 minutes. To the mixture was added a solution of 2,4,6-trimethoxyphenyl isocyanate (64.9 g, 0.310 mol) in THF (500 mL) over 10 minutes. Stirred 1.5 hours. The reaction was quenched with 1M HCl (310 mL, 0.310 mol) and allowed to warm to room temperature. The mixture was rotoevaporated to remove THF and partitioned between water and chloroform. The organic layer was washed (1M HCl; saturated NaCl), dried (Na2SO4), and rotoevaporated. The residue was chromatographed on silica gel (1.4 kg, 230-400 mesh) using petroleum ether-ethyl acetate (1:1). Fractions containing product were rotoevaporated, and the residue crystallized from ethanol-ether to give a white solid; yield 46.9 g (41%); mp 109°-111° C.

Workup

  1. stirringStirred 1.5 hours
  2. temperatureto warm to room temperature
  3. customto remove THF
  4. custompartitioned between water and chloroform
  5. washThe organic layer was washed (1M HCl; saturated NaCl)
  6. dry with materialdried (Na2SO4)
  7. customThe residue was chromatographed on silica gel (1.4 kg, 230-400 mesh)
  8. additionFractions containing product
  9. customthe residue crystallized from ethanol-ether
  10. customto give a white solid

Sources & evidence

ORD record
ord-c1a770ae610c4ee0a356f1a4ed14405c
Source dataset
uspto-grants-1995_08
Patent number
US05441975

Reaction notes

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