Hydrochloric Acid → 4-(3-Fluoro-5-((4-(2-methyl-1H-imidazol-1-YL)benzyl)oxy)phenyl)tetrahydro-2H-pyran-4-carboxylic acid

HRID 1418458Notes

Reaction equation

HRID 1418458 reaction equation
C([O:3][C:4]([C:6]1([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH:31]=[CH:30][N:29]=[C:28]4[CH3:32])=[CH:23][CH:22]=3)[CH:13]=2)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)=[O:5])C.[OH-].[Li+].CO.Cl>C1COCC1>[F:18][C:16]1[CH:15]=[C:14]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[CH:30][N:29]=[C:28]3[CH3:32])=[CH:23][CH:22]=2)[CH:13]=[C:12]([C:6]2([C:4]([OH:5])=[O:3])[CH2:7][CH2:8][O:9][CH2:10][CH2:11]2)[CH:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 11339601HCID 11339601, compound

Product 1

HCID 113158374-(3-Fluoro-5-((4-(2-methyl-1H-imidazol-1-YL)benzyl)oxy)phenyl)tetrahydro-2H-pyran-4-carboxylic acidYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A stirred mixture of ethyl 4-[5-fluoro-3-[4-(2-methylimidazol-1-yl)benzyloxy]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxylate (Example 2) (1.10 g, 25 mmol), an aqueous solution of lithium hydroxide (0.13 g, 30 mmol, 5 ml), methanol (15 ml) and THF (15 ml) was refluxed for 24 hr. The reaction mixture was neutralized with 1N hydrogen chloride. Volatiles were removed by evaporation under reduced pressure. The residue was suspended into a mixture of water (20 ml) and phosphate buffer (pH=7, 5 ml) and heated to reflux for 30 min. After cooling to 0° C., solids were collected by filtration, washed with water and then with ether and dried to constant weight under vacuum at 80° C. for 14 hr to afford the titled compound as white solids (0.98 g, 96%).

Workup

  1. customVolatiles were removed by evaporation under reduced pressure
  2. additionThe residue was suspended into a mixture of water (20 ml) and phosphate buffer (pH=7, 5 ml)
  3. temperatureheated
  4. temperatureto reflux for 30 min
  5. filtrationsolids were collected by filtration
  6. washwashed with water
  7. dry with materialwith ether and dried to constant weight under vacuum at 80° C. for 14 hr

Sources & evidence

ORD record
ord-2bb8d3cffb724501960800611f26c8ba
Source dataset
uspto-grants-1999_03
Patent number
US05883106

Reaction notes

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