Methyl iodide → N-(2-methylamino-5-iodobenzoyl)-b-alanine benzyl ester

HRID 1653861Notes

Reaction equation

HRID 1653861 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][NH:7][C:8](=[O:17])[C:9]1[CH:14]=[C:13]([I:15])[CH:12]=[CH:11][C:10]=1[NH2:16])[CH3:2].N1C(C)=[CH:23][CH:22]=[CH:21][C:20]=1[CH3:26].[CH3:27]I>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][NH:7][C:8](=[O:17])[C:9]1[CH:14]=[C:13]([I:15])[CH:12]=[CH:11][C:10]=1[NH:16][CH3:27])[C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:26]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 79372,6-LutidineHCID 10861356N-(2-amino-5-iodobenzoyl)-b-alanine ethyl ester

Product 1

HCID 22905394N-(2-methylamino-5-iodobenzoyl)-b-alanine benzyl esterYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A magnetically stirred solution of 0.848 gram of N-(2-amino-5-iodobenzoyl)-β-alanine ethyl ester (2.0 mmol), 0.35 mL 2,6-lutidine (3.0 mmol), 0.19 mL methyl iodide (3.0 mmol), and 15 mL dimethylformamide was heated to 50° C. for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated in vacuo. The resulting residue was disolved in 75 mL ethyl acetate and washed 1×50 mL 10% citric acid, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was further purified by column chromatography, using silica gel, eluting with a solvent gradient of 35/65 ethyl acetate/hexane to 65/35 ethyl acetate/hexane (TLC, SiO2, 1:1 EtOAc/hexane, Rf =0.84, υv positive) to yield 305 mgs (35%) of N-(2-methylamino-5-iodobenzoyl)-β-alanine benzyl ester. 1H NMR (CDCl3, dTMS) 7.56 (2H, m, Ar--H o,p--CON), 7.43 (1H, bq, 3JHH =5 Hz, NHMe), 7.38-7.32 (5H, s, ArH Ph), 6.62 (1H, bt, 3JHH =6 Hz, CONH), 6.42 (1H, d, 3JHH =9 Hz, Ar--H m--CON), 5.16 (2H, s, OCH2), 3.64 (2H, q, 3JHH =6 Hz, NCH2), 2.81 (3H, d, 3JHH =5 Hz, NCH3), 2.64 (2H, t, 3JHH =6 Hz, CH2CO2). 13C NMR (CDCl3, δTMS) 172.4, 168.4, 148.8, 141.0, 135.5, 128.7, 128.4, 128.3, 117.3, 113.4, 74.1, 66.7, 35.2, 34.0, 29.6.

Workup

  1. concentrationconcentrated in vacuo
  2. washwashed 1×50 mL 10% citric acid, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting oil was further purified by column chromatography
  7. washeluting with a solvent gradient of 35/65 ethyl acetate/hexane to 65/35 ethyl acetate/hexane (TLC, SiO2, 1:1 EtOAc/hexane, Rf =0.84, υv positive)

Sources & evidence

ORD record
ord-055018432c3e48d9adb1cf79611e4be6
Source dataset
uspto-grants-1995_04
Patent number
US05403836

Reaction notes

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