Sodium Hydroxide → 5-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid

HRID 2204297Notes

Reaction equation

HRID 2204297 reaction equation
[OH-].[Na+].C[O:4][C:5]([C:7]1[CH:11]=[C:10]([Br:12])[N:9]([CH:13]([CH3:15])[CH3:14])[C:8]=1[CH:16]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[C:27]([Cl:32])[CH:26]=1)[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)=[O:6]>C1COCC1.CO>[Br:12][C:10]1[N:9]([CH:13]([CH3:15])[CH3:14])[C:8]([CH:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[C:27]([Cl:32])[CH:26]=2)[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[C:7]([C:5]([OH:6])=[O:4])[CH:11]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 867031005-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester

Product 1

HCID 867030995-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

2N aqueous NaOH (32 mmol) was added to a solution of 5-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester (Step D2) (1.517 mmol) in 1:1 THF/MeOH (32 mL) and the mixture was stirred at 80° C. for 10 h. After evaporation of MeOH, the pH was adjusted to 5 with addition of 10% w/w aqueous citric acid (35 mL) and extracted with EtOAc. The organic phase was dried (Na2SO4), filtered and concentrated to afford a light brown solid. tR: 8.05 min (HPLC 2); ESI-MS: tR=1.38 min, [M−H] 497/499/501 (LC-MS 2).

Workup

  1. customAfter evaporation of MeOH
  2. additionthe pH was adjusted to 5 with addition of 10% w/w aqueous citric acid (35 mL)
  3. extractionextracted with EtOAc
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a light brown solid

Sources & evidence

ORD record
ord-33532a629c694578be133e7fc3fbd0f9
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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