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

HRID 1686217Notes

Reaction equation

HRID 1686217 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-864a0e5f9b114dee98a49fc930ea4358
Source dataset
uspto-grants-2012_04
Patent number
US08148544B2

Reaction notes

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