Potassium Iodide → N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]3-(thiophene-2-carbonyl)amino-L-alanine, [(ethoxycarbonyl)oxy]methyl ester

HRID 393112Notes

Reaction equation

HRID 393112 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([C:24]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([OH:34])[CH:29]=2)=[O:25])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C@H:7]([C:17]([OH:19])=[O:18])[CH2:8][NH:9][C:10]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[O:11])=[O:5].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[C:43](=[O:50])([O:47][CH2:48][CH3:49])[O:44][CH2:45]Cl>CN(C)C=O>[Cl:1][C:2]1[CH:23]=[C:22]([C:24]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([OH:34])[CH:29]=2)=[O:25])[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C@H:7]([C:17]([O:19][CH2:45][O:44][C:43]([O:47][CH2:48][CH3:49])=[O:50])=[O:18])[CH2:8][NH:9][C:10]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[O:11])=[O:5]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 5325479Chloromethyl Ethyl CarbonateHCID 60115134N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine

Product 1

HCID 58862078N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]3-(thiophene-2-carbonyl)amino-L-alanine, [(ethoxycarbonyl)oxy]methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine (Example 303; 1 mmol), potassium carbonate (1.1 mmol), potassium iodide (0.2 mmol), and chloromethyl ethyl carbonate (which is prepared according to Boehme, H. et al. Synthesis 1971, 588-590; 1.1 mmol) in N,N-dimethylformamide (10 mL) is heated at 60° C. for 3 h. The reaction mixture is concentrated to remove N,N-dimethylformamide. Water (50 mL) is added and the mixture is extracted with ethyl acetate (3×50 mL). The combined ethyl acetate layers are washed with brine (100 mL), dried (MgSO4), filtered, evaporated and chromatographed to give N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine, [(ethoxycarbonyl)oxy]methyl ester.

Workup

  1. concentrationThe reaction mixture is concentrated
  2. customto remove N,N-dimethylformamide
  3. additionWater (50 mL) is added
  4. extractionthe mixture is extracted with ethyl acetate (3×50 mL)
  5. washThe combined ethyl acetate layers are washed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed

Sources & evidence

ORD record
ord-81b9dc229e8b4580a586b7f1120c1bc3
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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