Pyridine → 4-Benzoyl-6-chloro-3-fluorenylmethoxycarbonylaminobenzoic acid

HRID 1077996Notes

Reaction equation

HRID 1077996 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]([Cl:19])=[CH:9][C:10]=1[C:11](=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:5]([OH:7])=[O:6].Cl[Si](C)(C)C.N1C=CC=CC=1.[C:31]1([CH2:44][O:45][C:46](Cl)=[O:47])[C:43]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]=2[CH:34]=[CH:33][CH:32]=1>C(Cl)Cl.C(OCC)(=O)C.CCCCCC.C(O)(=O)C.C(OCC)(=O)C>[C:11]([C:10]1[CH:9]=[C:8]([Cl:19])[C:4]([C:5]([OH:7])=[O:6])=[CH:3][C:2]=1[NH:1][C:46]([O:45][CH2:44][C:31]1[C:43]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]=2[CH:34]=[CH:33][CH:32]=1)=[O:47])(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 6397ChlorotrimethylsilaneHCID 124552493-Amino-4-benzoyl-6-chlorobenzoic acidHCID 14261773Fluorenylmethyl chloroformate

Product 1

HCID 194300344-Benzoyl-6-chloro-3-fluorenylmethoxycarbonylaminobenzoic acidYield 64%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 21901998Ethyl acetate hexane acetic acidSolvent

Conditions

Temperature
0 °C

Procedure

A solution was prepared by diluting 3-amino-4-benzoyl-6-chlorobenzoic acid (5.59 g, 20.3 mmol) with approximately 70 mL of CH2Cl2. Chlorotrimethylsilane (5.50 g, 51 mmol, 2.5 equivalents) was added by syringe and the resulting white slurry was heated at gentle reflux for 1.5 hours. After cooling the mixture to 0° C., pyridine (3.69 g, 46.7 mmol, 2.3 equivalents) was added by syringe, immediately followed by addition of fluorenylmethoxycarbonyl chloride (5.78 g, 22.3 mmol, 1.1 equivalents). The resulting slurry was stirred for one hour under a nitrogen atmosphere. The reaction solution was then diluted with CH2Cl2 (150 mL) and was extracted three times with 1.0N aqueous sodium bisulfate (100 mL) and once with aqueous sodium chloride (100 mL), then dried over sodium sulfate and concentrated in vacuo to give a viscous oil. Pure product was obtained in 64% yield (6.50 g) as a white solid by flash chromatography with 5 cm×25 cm silica gel and 40:60 ethyl acetate and then 75:25:1 ethyl acetate/hexane/acetic acid as the eluent. The structure was confirmed by proton NMR, carbon-13NMR, and FAB mass spectroscopy.

Workup

  1. customA solution was prepared
  2. temperaturethe resulting white slurry was heated
  3. temperatureat gentle reflux for 1.5 hours
  4. extractionwas extracted three times with 1.0N aqueous sodium bisulfate (100 mL)
  5. dry with materialonce with aqueous sodium chloride (100 mL), then dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a viscous oil

Sources & evidence

ORD record
ord-698c69bc571d493cb9de032637b3c288
Source dataset
uspto-grants-1996_08
Patent number
US05545568

Reaction notes

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