Pyridine → HCID 59432341, compound

HRID 507049Notes

Reaction equation

HRID 507049 reaction equation
Cl[C:2]([O:4][CH:5]([CH3:7])[CH3:6])=[O:3].C1(C)C=CC=CC=1.[CH3:15][O:16][C:17](=[O:31])[C:18]1[CH:23]=[C:22]([CH:24]=[CH2:25])[C:21]([C:26]([F:29])([F:28])[F:27])=[CH:20][C:19]=1[NH2:30].N1C=CC=CC=1>C(Cl)Cl>[CH3:15][O:16][C:17](=[O:31])[C:18]1[CH:23]=[C:22]([CH:24]=[CH2:25])[C:21]([C:26]([F:28])([F:27])[F:29])=[CH:20][C:19]=1[NH:30][C:2]([O:4][CH:5]([CH3:7])[CH3:6])=[O:3]

Participants

6

Reactant 4

HCID 1049PyridineHCID 1140TolueneHCID 7917Isopropyl chloroformateHCID 594324892-Amino-4-trifluoromethyl-5-vinyl-benzoic acid methyl ester

Product 1

HCID 59432341HCID 59432341, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Add a 1.0 M solution of isopropyl chloroformate in toluene (183.0 mL, 183.0 mmol) to a 0° C. cooled solution of 2-amino-4-trifluoromethyl-5-vinyl-benzoic acid methyl ester (34.47 g, 140.58 mmol) and pyridine (35.0 mL, 429.20 mmol) in methylene chloride (500 mL). Allow the mixture to stir for 2 h at 0° C. then 16 h at room temperature under an atmosphere of N2. Wash the mixture with saturated aqueous sodium bicarbonate solution (2×200 mL) followed by aqueous 2 N HCl solution (2×200 mL). Wash the combined organic extracts with brine (20 mL) and dry over anhydrous sodium sulfate. Remove the solvents under reduced pressure and purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (0 to 15%), to provide the title compound as an off-white solid (40.50 g, 87%): TLC Rf 0.62 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.32-1.33 (m, 6H), 3.89 (s, 3H), 5.21-5.27 (m, 1H), 5.41-5.44 (m, 1H), 5.63-5.70 (m, 1H), 7.03-7.11 (m, 1H), 8.23 (s, 1H), 8.89 (s, 1H), 10.32 (bs, 1H).

Workup

  1. custom16 h
  2. customat room temperature
  3. washWash the mixture with saturated aqueous sodium bicarbonate solution (2×200 mL)
  4. washWash the combined organic extracts with brine (20 mL)
  5. dry with materialdry over anhydrous sodium sulfate
  6. customRemove the solvents under reduced pressure
  7. custompurify the residue by column chromatography on silica gel
  8. washeluting with ethyl acetate/hexanes (0 to 15%)

Sources & evidence

ORD record
ord-131185cfea724da4be83fc40f9636212
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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