Sodium Hydroxide → 4-{2-[4-({[2-({3-[(4-Carboxybutyl)(cyclopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid

HRID 926084Notes

Reaction equation

HRID 926084 reaction equation
[CH:1]1([N:4]([CH2:47][CH2:48][CH2:49][CH2:50][C:51]([O:53]C)=[O:52])[S:5]([C:8]2[CH:9]=[C:10]([CH:44]=[CH:45][CH:46]=2)[C:11]([NH:13][C:14]2[S:15][C:16]3[CH2:43][CH2:42][CH2:41][CH2:40][C:17]=3[C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]3[CH:39]=[CH:38][C:33]([C:34]([O:36]C)=[O:35])=[CH:32][CH:31]=3)=[CH:24][CH:23]=2)=[O:20])=[O:12])(=[O:7])=[O:6])[CH2:3][CH2:2]1.[OH-].[Na+]>C(O)C>[C:51]([CH2:50][CH2:49][CH2:48][CH2:47][N:4]([CH:1]1[CH2:2][CH2:3]1)[S:5]([C:8]1[CH:9]=[C:10]([CH:44]=[CH:45][CH:46]=1)[C:11]([NH:13][C:14]1[S:15][C:16]2[CH2:43][CH2:42][CH2:41][CH2:40][C:17]=2[C:18]=1[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]2[CH:31]=[CH:32][C:33]([C:34]([OH:36])=[O:35])=[CH:38][CH:39]=2)=[CH:24][CH:23]=1)=[O:20])=[O:12])(=[O:6])=[O:7])([OH:53])=[O:52]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68207813Methyl 4-{2-[4-({[2-({3-[cyclopropyl(5-methoxy-5-oxopentyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate

Product 1

HCID 545885834-{2-[4-({[2-({3-[(4-Carboxybutyl)(cyclopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acidYield 81.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 208 mg of methyl 4-{2-[4-({[2-({3-[cyclopropyl(5-methoxy-5-oxopentyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate, 1.5 mL of a 1.0 M aqueous sodium hydroxide solution, and 2.1 mL of ethanol was heated and refluxed overnight. The reaction mixture was concentrated under reduced pressure, and then to the obtained residue were added water, 300 mg of citric acid, dichloromethane, and THF in this order, and the organic layer was separated and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol). The crude product was washed with diethyl ether to obtain 163 mg of 4-{2-[4-({[2-({3-[(4-carboxybutyl)(cyclopropyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoic acid as a colorless crystal.

Workup

  1. temperaturewas heated
  2. temperaturerefluxed overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionto the obtained residue were added water, 300 mg of citric acid, dichloromethane, and THF in this order
  5. customthe organic layer was separated
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (chloroform-methanol)
  8. washThe crude product was washed with diethyl ether

Sources & evidence

ORD record
ord-59c1877a61d24a18a97021da8501aa3e
Source dataset
uspto-grants-2016_03
Patent number
US09284295B2

Reaction notes

Loading…