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

HRID 1655687Notes

Reaction equation

HRID 1655687 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 dissolved 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, υν 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 (2 H, 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. dissolutionThe resulting residue was dissolved in 75 mL ethyl acetate
  3. washwashed 1×50 mL 10% citric acid, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting oil was further purified by column chromatography
  8. 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, υν positive)

Sources & evidence

ORD record
ord-82aafb3ed71d4dc6b53bec41bfbfca23
Source dataset
uspto-grants-1993_10
Patent number
US05250679

Reaction notes

Loading…