Water → (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]3-[2-ethyl-4-(1-methylethyl)thiazole-5-yl]propenoic acid methyl ester

HRID 1058426Notes

Reaction equation

HRID 1058426 reaction equation
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11](=[O:40])[CH:12](P(OC)(OC)=O)[NH:13][C:14](=[O:33])[C:15]1[CH:20]=[CH:19][C:18]([C:21]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:22])=[CH:17][C:16]=1[Cl:32].[CH2:41]([C:43]1[S:44][C:45]([CH:51]=O)=[C:46]([CH:48]([CH3:50])[CH3:49])[N:47]=1)[CH3:42].O>ClCCl>[CH3:9][O:10][C:11](=[O:40])/[C:12](/[NH:13][C:14](=[O:33])[C:15]1[CH:20]=[CH:19][C:18]([C:21]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:22])=[CH:17][C:16]=1[Cl:32])=[CH:51]/[C:45]1[S:44][C:43]([CH2:41][CH3:42])=[N:47][C:46]=1[CH:48]([CH3:49])[CH3:50]

Participants

6

Reactant 4

HCID 962WaterHCID 664601,1,3,3-TetramethylguanidineHCID 186730422-Ethyl-4-(1-methylethyl)thiazole-5-carboxaldehydeHCID 23560750HCID 23560750, compound

Product 1

HCID 59038402(Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]3-[2-ethyl-4-(1-methylethyl)thiazole-5-yl]propenoic acid methyl esterYield 65.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

1,1,3,3-Tetramethylguanidine (107 mg, 0.93 mmol) was added to a solution of rac.-N-[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (Example 141; 300 mg, 0.62 mmol) in dichloromethane (10 mL) at ˜5° C. The solution was stirred at ˜5° C. for 30 min and then 2-ethyl-4-(1-methylethyl)thiazole-5-carboxaldehyde (Example 61; 224 mg, 1.24 mmol) was added. The solution was stirred over a weekend at room temperature, then water was added and the layers were separated. The aqueous layer was extracted with two portions of dichloromethane then the combined organic layers were washed in turn with brine, 0.5N hydrochloric acid solution, water and brine. The dried (MgSO4) organic extracts were evaporated and the resulting oil was purified by chromatography over silica gel. Evaporation of the appropriate fractions afforded (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoyl]amino]3-[2-ethyl-4-(1-methylethyl)thiazole-5-yl]propenoic acid methyl ester (220 mg, 65% yield).

Workup

  1. stirringThe solution was stirred over a weekend at room temperature
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with two portions of dichloromethane
  4. washthe combined organic layers were washed in turn with brine, 0.5N hydrochloric acid solution, water and brine
  5. dry with materialThe dried (MgSO4) organic extracts
  6. customwere evaporated
  7. customthe resulting oil was purified by chromatography over silica gel
  8. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-825b7c337fc04cdc8b833ea8d519bf0b
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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