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

HRID 926067Notes

Reaction equation

HRID 926067 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([N:9]([CH:52]([CH3:54])[CH3:53])[S:10]([C:13]2[CH:14]=[C:15]([CH:49]=[CH:50][CH:51]=2)[C:16]([NH:18][C:19]2[S:20][C:21]3[CH2:48][CH2:47][CH2:46][CH2:45][C:22]=3[C:23]=2[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]3[CH:44]=[CH:43][C:38]([C:39]([O:41]C)=[O:40])=[CH:37][CH:36]=3)=[CH:29][CH:28]=2)=[O:25])=[O:17])(=[O:12])=[O:11])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[OH-].[Na+]>C(O)C>[CH2:1]([O:3][C:4]([C:6]1([N:9]([CH:52]([CH3:53])[CH3:54])[S:10]([C:13]2[CH:14]=[C:15]([CH:49]=[CH:50][CH:51]=2)[C:16]([NH:18][C:19]2[S:20][C:21]3[CH2:48][CH2:47][CH2:46][CH2:45][C:22]=3[C:23]=2[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35]3[CH:44]=[CH:43][C:38]([C:39]([OH:41])=[O:40])=[CH:37][CH:36]=3)=[CH:29][CH:28]=2)=[O:25])=[O:17])(=[O:12])=[O:11])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 71238705Methyl 4-(2-{4-[({2-[(3-{[1-(ethoxycarbonyl)cyclopropyl](isopropyl)sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoate

Product 1

HCID 682077874-(2-{4-[({2-[(3-{[1-(Ethoxycarbonyl)cyclopropyl](isopropyl)sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoic acidYield 59.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 290 mg of methyl 4-(2-{4-[({2-[(3-{[1-(ethoxycarbonyl)cyclopropyl](isopropyl)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 2.9 mL of ethanol was heated and refluxed overnight. The reaction mixture was concentrated under reduced pressure, and to the residue were added water, citric acid, dichloromethane, and THF in this order. The organic layer was separated and then concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform-methanol). The crude purified product thus obtained was washed with diethyl ether to obtain 169 mg of 4-(2-{4-[({2-[(3-{[1-(ethoxycarbonyl)cyclopropyl](isopropyl)sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoic acid as a pale yellow solid.

Workup

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

Sources & evidence

ORD record
ord-05fdca97d8da4481a9918d89157ba6a9
Source dataset
uspto-grants-2016_03
Patent number
US09284295B2

Reaction notes

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