2-Dimethylaminopyridine → N-(2-amino-5-iodobenzoyl)-beta-alanine benzyl ester

HRID 1653860Notes

Reaction equation

HRID 1653860 reaction equation
[I:1][C:2]1[CH:13]=[C:6]2[C:7](OC(=O)[NH:11][C:5]2=[CH:4][CH:3]=1)=[O:8].S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH2:25]([O:32][C:33](=[O:37])[CH2:34][CH2:35][NH2:36])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CN(C1C=CC=CN=1)C>N1C=CC=CC=1>[CH2:25]([O:32][C:33](=[O:37])[CH2:34][CH2:35][NH:36][C:7](=[O:8])[C:6]1[CH:13]=[C:2]([I:1])[CH:3]=[CH:4][C:5]=1[NH2:11])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 218852-DimethylaminopyridineHCID 2944806-iodo-2H-3,1-benzoxazine-2,4(1H)-dioneHCID 135021004-Methylbenzene-1-sulfonic acid--benzyl beta-alaninate (1/1)

Product 1

HCID 22905047N-(2-amino-5-iodobenzoyl)-beta-alanine benzyl esterYield 25.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A magnetically stirred solution of 5 grams of 5-iodoisatoic anhydride (0.0173 mol), 5.85 grams of β-alanine benzyl ester tosylate (0.0173 mol), 35 mL pyridine, and 0.5 of dimethylaminopyridine (0.0041 mol) was heated to 80° C. for 2 hrs. The reaction mixture was allowed to cool to room temperature and concentrated in vacuo. The resulting residue was dissolved in 100mL ethyl acetate and washed 2×50 mL of 10% cupric sulfate, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine, dried over sodium sulfate, filtered and concentrated in vacuo. The product was further purified by column chromatography, using silica gel, eluting with a 1:1 mixture of ethyl acetate and hexane (TLC, SIO2, 1:1 EtOAc/hexane, Rf =0.65, υν positive) to yield 1.85 grams (25%) of N-(2-amino-5-iodobenzoyl)-β-alanine benzyl ester. 1H NMR (CDCl3, δTMS) 7.54 (1H, d, 4JHH =2 Hz, Ar--H o--CON), 7.42 (1H, dd, 3JHH =9 Hz, 4JHH =2 Hz, Ar--H p--CON), 7.38-7.32 (5H, s, ArH Ph), 6.65 (1H, bt, 3JHH =6 Hz, CONH), 6.46 (1H, d, 3JHH =9 Hz, Ar--H m--CON), 5.16 (2H, s, OCH2), 3.68 (2H, q, 3JHH =6 Hz, NCH2), 2.69 (2H, t, 3JHH =6 Hz, CH2CO2). 13C NMR (CDCl3,δTMS) 172.4, 167.8, 148.2, 140.6, 135.6, 135.5, 128.7, 128.4, 128.3, 119.3, 118.1, 76.3, 66.7, 35.2, 34.0.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in 100mL ethyl acetate
  3. washwashed 2×50 mL of 10% cupric sulfate, 1×50 mL sat. sodium bicarbonate, 1×50 mL brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was further purified by column chromatography
  8. washeluting with a 1:1 mixture of ethyl acetate and hexane (TLC, SIO2, 1:1 EtOAc/hexane, Rf =0.65, υν positive)

Sources & evidence

ORD record
ord-78786f77def64576b6734d6b0fa289d4
Source dataset
uspto-grants-1995_04
Patent number
US05403836

Reaction notes

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