Sodium Hydroxide → 4-(N-(4-fluorobenzyl)-N-(4-methoxybenzyl)sulfamoyl)benzoic acid

HRID 1770441Notes

Reaction equation

HRID 1770441 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][N:7]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[S:8]([C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17]C)=[O:16])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[OH-].[Na+]>CO.C1COCC1>[F:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][N:7]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[S:8]([C:11]2[CH:12]=[CH:13][C:14]([C:15]([OH:17])=[O:16])=[CH:19][CH:20]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 57422334Methyl 4-(N-(4-fluorobenzyl)-N-(4-methoxybenzyl)sulfamoyl)benzoate

Product 1

HCID 252053594-(N-(4-fluorobenzyl)-N-(4-methoxybenzyl)sulfamoyl)benzoic acidYield 58.9%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

Methyl 4-(N-(4-fluorobenzyl)-N-(4-methoxybenzyl)sulfamoyl)benzoate (Example 5-10a) (3.7 g, 8.3 mmol) was dissolved in MeOH/THF (1:1.5, 30 mL) and treated with aqueous NaOH (3 N, 15 mL). The mixture was stirred at ambient temperature overnight, then MeOH and THF were removed in vacuo. The resulting aqueous solution was acidified with 6 N aq HCl to a pH of ˜3 and extracted with EtOAc (3×40 mL). The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated. The crude product was purified by recrystallization from EtOH to afford pure 4-(N-(4-fluorobenzyl)-N-(4-methoxybenzyl)sulfamoyl)benzoic acid as a white crystalline solid (2.1 g, 58.6%). MS (M−H, 428.1); 1H NMR (400 MHz, DMSO-d6): δ, ppm: 3.66 (s, 3H), 4.23 (s, 2H), 4.26 (s, 2H), 6.72 (d, 2H, J=8 Hz), 6.95 (m, 6H), 7.92 (d, 2H J=8 Hz), 8.07 (d, 2H, J=8 Hz). The compound had an IC50 on hT2R14 bitter receptor of 1.97 μM.

Workup

  1. customMeOH and THF were removed in vacuo
  2. extractionextracted with EtOAc (3×40 mL)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by recrystallization from EtOH

Sources & evidence

ORD record
ord-92f824297720404a9fbca07b48d6470d
Source dataset
uspto-grants-2016_02
Patent number
US09247759B2

Reaction notes

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