Lithium Hydroxide → HCID 90405670, compound

HRID 2167388Notes

Reaction equation

HRID 2167388 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])[CH:5]=[C:6]([F:25])[C:7]=1[O:8][CH2:9][C:10]1[N:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:13][C:14]=1[C:15]([F:18])([F:17])[F:16].O1CCCC1.[Li+].[OH-]>O>[F:1][C:2]1[CH:3]=[C:4]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])[CH:5]=[C:6]([F:25])[C:7]=1[O:8][CH2:9][C:10]1[N:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:13][C:14]=1[C:15]([F:18])([F:16])[F:17]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 90406160HCID 90406160, compound

Product 1

HCID 90405670HCID 90405670, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

Into a 25-mL round-bottom flask, was placed ethyl 3-(3,5-difluoro-4-[[1-phenyl-3-(trifluoromethyl)-1H-pyrrol-2-yl]methoxy]phenyl)propanoate (100 mg, 0.22 mmol, 1.00 equiv), tetrahydrofuran (1 mL) and a solution of LiOH (100 mg, 4.18 mmol, 18.93 equiv) in water (1 mL). The resulting solution was stirred overnight at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was then concentrated under vacuum. The pH value of the solution was adjusted to pH5 with hydrogen chloride (2 mol/L). The resulting solution was extracted with ethyl acetate (3×5 mL) and the organic layers combined. The resulting residue was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ACN/H2O (0.05% CF3COOH)=1:1 increasing to ACN/H2O (0.05% CF3COOH)=9:1 within 10 min; Detector, UV 254 nm to yield 3-(3,5-difluoro-4-[[1-phenyl-3-(trifluoromethyl)-1H-pyrrol-2-yl]methoxy]phenyl)propanoic acid as a white solid (22.5 mg, 23%).

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was then concentrated under vacuum
  3. extractionThe resulting solution was extracted with ethyl acetate (3×5 mL)
  4. customThe resulting residue was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  5. waitmobile phase, ACN/H2O (0.05% CF3COOH)=1:1 increasing to ACN/H2O (0.05% CF3COOH)=9:1 within 10 min

Sources & evidence

ORD record
ord-a8235078f7094e41a4e9800a406dec54
Source dataset
uspto-grants-2015_06
Patent number
US09045454B2

Reaction notes

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