Triethylamine → Ethyl 4-(4-benzylbenzamido)-3-fluorobenzoate

HRID 658976Notes

Reaction equation

HRID 658976 reaction equation
[CH2:1]([C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:30][C:31]1[CH:41]=[CH:40][C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:33][C:32]=1[F:42]>ClCCl.CN(C=O)C>[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([C:12]([NH:30][C:31]2[CH:41]=[CH:40][C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:33][C:32]=2[F:42])=[O:14])=[CH:15][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1364294-Benzylbenzoic acidHCID 20536493Ethyl 4-amino-3-fluorobenzoate

Product 1

HCID 57625194Ethyl 4-(4-benzylbenzamido)-3-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 4-benzylbenzoic acid (1.06 g, 5 mmole) in dichloromethane (10 mL) was added oxalyl dichloride (1 mL) followed by a few drops of DMF at 0° C. The resulting mixture was stirred room temperature for 3 hours. Removal of the solvents gave the residue which was dissolved in dichloromethane (2 mL) and added to the solution of triethylamine (1.4 mL, 10 mmol) and ethyl 4-amino-3-fluorobenzoate (916 mg, 5 mmole) in dichloromethane (50 mL) at 0° C. After stirring at room temperature for 48 hours, the mixture was washed with saturated sodium bicarbonate and 1 N HCl. The combined organic extracts were washed with brine, dried and concentrated under reduced pressure to give the residue which was purification by silica gel chromatography on ISCO system. The desired product was obtained as an off white solid: 1H NMR (400 MHz, CDCl3) δ 8.63 (t, J=8.8 Hz, 1H), 8.20 (s, 1H), 7.83 (m, 4H), 7.18-7.35 (m, 6H), 4.39 (q, J=7.2 Hz, 1H), 4.07 (s, 2H), 1.40 (t, J=7.2 Hz, 3H).

Workup

  1. customRemoval of the solvents
  2. customgave the residue which
  3. stirringAfter stirring at room temperature for 48 hours
  4. washthe mixture was washed with saturated sodium bicarbonate and 1 N HCl
  5. washThe combined organic extracts were washed with brine
  6. customdried
  7. concentrationconcentrated under reduced pressure
  8. customto give the residue which
  9. custompurification by silica gel chromatography on ISCO system

Sources & evidence

ORD record
ord-34960b9d0fe3479db2e3eec0dfe574f4
Source dataset
uspto-grants-2011_12
Patent number
US08080542B2

Reaction notes

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