Benzaldehyde → HCID 69307715, compound

HRID 2056639Notes

Reaction equation

HRID 2056639 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([NH2:14])[CH:7]=1)[CH3:2].[CH:16](=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([N-]C(C)C)(C)C.[Li+].[N+:32]([C:35]1[CH:42]=[CH:41][C:38]([CH2:39]Br)=[CH:37][CH:36]=1)([O-:34])=[O:33]>C1(C)C=CC=CC=1.O1CCCC1>[CH2:1]([O:3][C:4](=[O:15])[CH:5]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([N:14]=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:7]=1)[CH2:39][C:38]1[CH:41]=[CH:42][C:35]([N+:32]([O-:34])=[O:33])=[CH:36][CH:37]=1)[CH3:2]

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 660114-Nitrobenzyl bromideHCID 2724682Lithium diisopropylamideHCID 63021771Ethyl 3-amino-4-methoxybenzeneacetate

Product 1

HCID 69307715HCID 69307715, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

Thus obtained 3-amino-4-methoxyphenylacetic acid ethyl ester (6.06 g, 29 mmol) was dissolved in toluene (200 mL), added with benzaldehyde (2.94 mL, 29 mmol), and refluxed under heating at 130° C. for 14 hours. The reaction mixture was cooled to room temperature, evaporated under reduced pressure so as to remove the solvent, and the resultant residue was dissolved in tetrahydrofuran (200 mL), and added drop-wisely with a 2 mol/L lithium diisopropylamide solution (heptane/tetrahydrofuran/ethylbenzene solution, 15.9 mL, 32 mmol) while keeping the temperature thereof at −78° C. The mixture was heated to −20° C., stirred for 10 minutes, cooled again to −78° C., and at that temperature added drop-wisely with a tetrahydrofuran solution (80 mL) of 4-nitrobenzyl bromide (6.88 g, 32 mmol). The mixture was then heated to room temperature, and 2-[3-(benzylideneamino)-4-methoxy phenyl]-3-(4-nitrophenyl)propionic acid ethyl ester was produced in the reaction solution. Next as a series of processing, the reaction solution was then treated with a 1 mol/L hydrochloric acid (150 mL), the separated aqueous phase was added with an aqueous saturated sodium hydrogen carbonate solution so as to adjust pH of the solution as high as 7 or above, and extracted with ethyl acetate, which series was repeated three times. The ethyl acetate phase was dried over anhydrous sodium sulfate, evaporated under reduced pressure so as to remove the solvent, and the resultant residue was purified through silica gel column chromatography (hexane:ethyl acetate (v/v)=2:1) to thereby obtain 2-(3-amino-4-methoxyphenyl)-3-(4-nitrophenyl)propionic acid ethyl ester (yield: 5.63 g, yield ratio: 56%) as an orange syrup.

Workup

  1. temperaturerefluxed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customevaporated under reduced pressure so as
  4. customto remove the solvent
  5. dissolutionthe resultant residue was dissolved in tetrahydrofuran (200 mL)
  6. customat −78° C
  7. temperatureThe mixture was heated to −20° C.
  8. temperaturecooled again to −78° C.
  9. temperatureThe mixture was then heated to room temperature

Sources & evidence

ORD record
ord-54ae32aae6694d18acfa0a1a5c89d782
Source dataset
uspto-grants-2008_02
Patent number
US07335673B2

Reaction notes

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