4-Chlorobenzaldehyde → N-(5-(4-cyanobenzyloxy)-2-(4-chlorobenzylamino)benzoyl)-b-alanine ethyl ester

HRID 865350Notes

Reaction equation

HRID 865350 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[CH2:5][CH2:6][NH:7][C:8](=[O:26])[C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=2)[CH:12]=[CH:11][C:10]=1[NH2:25])[CH3:2].[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH:33]=O)=[CH:31][CH:30]=1.C([SiH](CC)CC)C>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][CH2:6][NH:7][C:8](=[O:26])[C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][CH:22]=2)[CH:12]=[CH:11][C:10]=1[NH:25][CH2:33][C:32]1[CH:35]=[CH:36][C:29]([Cl:28])=[CH:30][CH:31]=1)[CH3:2]

Participants

6

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 12052TriethylsilaneHCID 19700602HCID 19700602, compound

Product 1

HCID 22905094N-(5-(4-cyanobenzyloxy)-2-(4-chlorobenzylamino)benzoyl)-b-alanine ethyl esterYield 59.5%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Procedure

A solution of 1.03 g (2.80 mmol) of N-(5-(4-cyanobenzyloxy)-2-aminobenzoyl)-b-alanine ethyl ester, 394 mg (2.80 mmol) of p-chlorobenzaldehyde, and 20 mg of p-toluenesulfonic acid in 30 mL of toluene was heated at reflux through a Dean-Stark trap for 45 min. The solvent was removed in vacuo and the residue was dissolved in 15 mL of trifluoroacetic acid. Triethylsilane (1.34 mL, 8.40 mmol) was added and the mixture was stirred at room temperature for 12 h, concentrated in vacuo, and partitioned between 1N aqueous sodium bicarbonate and ethyl acetate. The organic phase was washed with water, brine, dried over anhydrous magnesium sulfate, and concentrated. Chromatography (silica gel-60, 2:3 ethyl acetate/hexane) gave 820 mg (59%) of N-(5-(4-cyanobenzyloxy)-2-(4-chlorobenzylamino)benzoyl)-b-alanine ethyl ester as a colorless solid. 1H NMR (300 MHz, CDCl3) d 7.66 (2H, d, J=7.8 Hz, NC-Ar-H2), 7.51 (2H, d, J=7.8 Hz, NC-Ar-H2), 7.27 (4H, s, ClArH4), 6.98 (1H, d, J=2.0 Hz, O-Ar-H), 6.89 (1H, dd, J=2.0, 9.3 Hz, O-Ar-H), 6.78 (1H, b, N-H), 6.66 (1H, d, J=9.3 Hz, O-Ar-H), 5.03 (2H, s, ArCH2O), 4.32 (2H, s, ClArCH2), 4.17 (2H, q, J=7.3 Hz, OCH2CH3), 3.65 (2H, bq, J=5.7 Hz, NHCH2CH2), 2.62 (2H, t, J=5.7 Hz, NHCH2CH2), 1.28 (3H, t, J=7.3 Hz, OCH2CH3); Exact mass (FAB, M+H+) calcd for C27H27ClN3O4 : 492.1690; Found: 492.1681.

Workup

  1. temperatureat reflux through a Dean-Stark trap for 45 min
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in 15 mL of trifluoroacetic acid
  4. concentrationconcentrated in vacuo
  5. custompartitioned between 1N aqueous sodium bicarbonate and ethyl acetate
  6. washThe organic phase was washed with water, brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-085c14cc37f540e2929efeeb46a2dc48
Source dataset
uspto-grants-1996_10
Patent number
US05565449

Reaction notes

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