Hydrochloric Acid → HCID 89767871, compound

HRID 591485Notes

Reaction equation

HRID 591485 reaction equation
C([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:10]2[CH:11]=[CH:12][C:13]([O:15][CH2:16][C:17]3[C:18]([Cl:24])=[N:19][C:20]([CH3:23])=[N:21][CH:22]=3)=[CH:14][C:9]=2[S:8][CH:7]=1)C.[Li+].[OH-].Cl>C1COCC1.CCO>[Cl:24][C:18]1[C:17]([CH2:16][O:15][C:13]2[CH:12]=[CH:11][C:10]3[C:6]([CH2:5][C:4]([OH:25])=[O:3])=[CH:7][S:8][C:9]=3[CH:14]=2)=[CH:22][N:21]=[C:20]([CH3:23])[N:19]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 118667016HCID 118667016, compound

Product 1

HCID 89767871HCID 89767871, compoundYield 27.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethyl(6-((4-chloro-2-methylpyrimidin-5-yl)methoxy)-1-benzothiophen-3-yl)acetate (70 mg) in THF (3 mL) and EtOH (2 mL) was added 4N LiOH (0.186 mL) at room temperature. The mixture was stirred at room temperature for 5 h. The mixture was neutralized with 1N HCl at room temperature and concentrated in vacuo. Water and saturated aqueous NH4Cl were poured into the residue and extracted with EtOAc. The organic layer was separated, dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC (C18, water/CH3CN (including 0.1% TFA)). The fraction including Example 72 was neutralized with saturated aqueous NaHCO3 and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residual solid was recrystallized from EtOAc-hexane to give (6-((4-chloro-2-methylpyrimidin-5-yl)methoxy)-1-benzothiophen-3-yl)acetic acid (Example 72, 18 mg). The fraction including Example 73 was neutralized with saturated aqueous NaHCO3 and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residual solid was recrystallized from EtOAc-hexane to give (6-((4-ethoxy-2-methylpyrimidin-5-yl)methoxy)-1-benzothiophen-3-yl)acetic acid (Example 73, 12.8 mg).

Workup

  1. concentrationconcentrated in vacuo
  2. additionWater and saturated aqueous NH4Cl were poured into the residue
  3. extractionextracted with EtOAc
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative HPLC (C18, water/CH3CN (including 0.1% TFA))
  8. extractionextracted with EtOAc
  9. washThe organic layer was washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe residual solid was recrystallized from EtOAc-hexane

Sources & evidence

ORD record
ord-fbb6c2658bc3406bb942386e8d0f737d
Source dataset
uspto-grants-2016_01
Patent number
US09238639B2

Reaction notes

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