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

HRID 2204292Notes

Reaction equation

HRID 2204292 reaction equation
C([O:3][C:4]([C:6]1[CH:10]=[CH:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:7]=1[CH:14]([NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[C:25]=1[F:31])[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[CH3:22])=[O:5])C.[Li+].[OH-]>O1CCOCC1>[Cl:30][C:26]1[C:25]([F:31])=[C:24]([NH:23][CH:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[CH3:22])[C:7]2[N:8]([CH:11]([CH3:13])[CH3:12])[CH:9]=[CH:10][C:6]=2[C:4]([OH:5])=[O:3])[CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 867030952-[(3-chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 867030942-[(3-chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-[(3-chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester (Step A3) (2.154 mmol) and 1N aqueous LiOH (8.62 mmol) in dioxane (25 mL) was heated at 100° C. for 26 h. After cooling to rt, the reaction mixture was partitioned between EtOAc and 10% w/w aqueous citric acid. The aqueous phase was extracted with EtOAc (2×). The combined organic phases were dried (Na2SO4), filtered and concentrated to afford the title compound as a pale yellow solid which was used in the next step without further purification. tR: 5.48 min (HPLC 1); ESI-MS: tR=1.33 min, [M−H] 433/435 (LC-MS 1).

Workup

  1. temperatureAfter cooling to rt
  2. customthe reaction mixture was partitioned between EtOAc and 10% w/w aqueous citric acid
  3. extractionThe aqueous phase was extracted with EtOAc (2×)
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-34087dfeaca74d07bd9c202a846011a7
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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