Chlorotrimethylsilane → 2-(4-(N-salicyloyl)aminophenyl)propionic acid

HRID 1371261Notes

Reaction equation

HRID 1371261 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:12])[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.C[Si](Cl)(C)C.C(N(CC)CC)C.CC([O:28][C:29]1[C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=[CH:31][CH:30]=1)=O>C(Cl)Cl>[C:35]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH3:12])[C:9]([OH:11])=[O:10])=[CH:6][CH:7]=1)(=[O:36])[C:34]1[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=1)[OH:28]

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 430264-Aminohydratropic acidHCID 796682-Acetoxybenzoyl chloride

Product 1

HCID 98173032-(4-(N-salicyloyl)aminophenyl)propionic acidYield 52.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A slurry of 58.6 g (0.355 mol) of 2-(4-aminophenyl)propionic acid and 500 ml of methylene chloride is treated with 90.11 ml (77.13 g. 0–710 mol) of trimethylsilyl chloride and is heated to reflux for 120 min. The reaction mixture is cooled to 0° C. and treated with 184.44 ml (107.77 g, 1.065 mol) of triethylamine. After stirring for 5 minutes, this mixture is treated with a solution of 70.45 g (0.355 mol) of O-acetylsalicyloyl chloride and 150 ml of methylene chloride. The reaction mixture is warmed to 25° C. and stirred for 64 hr. The volatiles are removed in vacuo. The residue is stirred in 2N aqueous sodium hydroxide for one hour and acidified with 2 M aqueous sulfuric acid. The solid is recrystallized twice from ethanol/water to give a tan solid. Isolation by filtration results in an expected yield of 53.05 g (52% yield) of 2-(4-(N-salicyloyl)aminophenyl)propionic acid. Properties. Solubility: 200 mg/m: 200 mg+350.μL 2N NaOH+650.μL H2O-pH-7.67. Analysis: C, 67.36; H, 5.3; N, 4.91.

Workup

  1. temperatureis heated
  2. temperatureto reflux for 120 min
  3. temperatureThe reaction mixture is warmed to 25° C.
  4. stirringstirred for 64 hr
  5. customThe volatiles are removed in vacuo
  6. stirringThe residue is stirred in 2N aqueous sodium hydroxide for one hour
  7. customThe solid is recrystallized twice from ethanol/water
  8. customto give a tan solid
  9. filtrationIsolation by filtration

Sources & evidence

ORD record
ord-367f8cd3ed5c412d914e5497ef03d2b4
Source dataset
uspto-grants-2007_01
Patent number
US07157426B2

Reaction notes

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