Sodium Hydroxide → HCID 178480530, compound

HRID 1372778Notes

Reaction equation

HRID 1372778 reaction equation
[Cl:1][C:2]1[C:3]([NH:31][C:32]([C:34]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[N:36]([CH3:43])[CH:35]=2)=[O:33])=[CH:4][C:5]([F:30])=[C:6]([CH2:8][C:9]([N:11]2[CH2:15][C:14]([F:17])([F:16])[CH2:13][C@H:12]2[CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH:23]([C:26]([O:28]C)=[O:27])[CH2:22][CH2:21]2)=[O:10])[CH:7]=1.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[C:3]([NH:31][C:32]([C:34]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[N:36]([CH3:43])[CH:35]=2)=[O:33])=[CH:4][C:5]([F:30])=[C:6]([CH2:8][C:9]([N:11]2[CH2:15][C:14]([F:16])([F:17])[CH2:13][C@H:12]2[CH2:18][O:19][C@H:20]2[CH2:25][CH2:24][C@H:23]([C:26]([OH:28])=[O:27])[CH2:22][CH2:21]2)=[O:10])[CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58778482HCID 58778482, compound

Product 1

HCID 178480530HCID 178480530, compoundYield 16.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To methyl 4-(1-(5-chloro-2-fluoro-4-(1-methyl-3-indolylcarbonylamino)phenylacetyl)-4,4-difluoro-(2S)-pyrrolidinylmethoxy)cyclohexanecarboxylate (620 mg, 0.53 mmol) were added THF (4.5 ml) and 0.25N NaOH (4.5 ml). The resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was distilled under reduced pressure to remove the solvent. The residue was acidified with 1N HCl, followed by extraction with chloroform-methanol (5:1, v/v). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and distilled under reduced pressure to remove the solvent. By chromatography using a silica gel thin-layer plate (Whatman TLC), two diastereomers were separated from the residue, whereby from chloroform-methanol (40:1, v/v×3) eluate fractions, trans-4-(1-(5-chloro-2-fluoro-4-(1-methyl-3-indolylcarbonylamino)phenylacetyl)-4,4-difluoro-(2S)-pyrrolidinylmethoxy)cyclohexanecarboxylic acid (53 mg, 16%) was obtained as a white solid.

Workup

  1. distillationThe reaction mixture was distilled under reduced pressure
  2. customto remove the solvent
  3. extractionfollowed by extraction with chloroform-methanol (5:1
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customwere separated from the residue, whereby from chloroform-methanol (40:1, v/v×3) eluate fractions

Sources & evidence

ORD record
ord-fbae16108e2247d8af3a9a9e21de8443
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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