Sodium Hydroxide → HCID 71547556, compound

HRID 523944Notes

Reaction equation

HRID 523944 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:44]=[CH:43][C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:26]=[C:27]([NH:29][C:30]([N:32]3[CH2:37][CH2:36][C:35]([OH:42])([CH2:38][CH:39]([CH3:41])[CH3:40])[CH2:34][CH2:33]3)=[O:31])[CH:28]=2)[O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([CH3:25])([CH3:24])[C:20]([O:22]C)=[O:21])=[CH:15][CH:14]=2)=[CH:6][CH:5]=1>CO.C1COCC1>[F:3][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:26]=[C:27]([NH:29][C:30]([N:32]3[CH2:33][CH2:34][C:35]([OH:42])([CH2:38][CH:39]([CH3:41])[CH3:40])[CH2:36][CH2:37]3)=[O:31])[CH:28]=2)[O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([CH3:24])([CH3:25])[C:20]([OH:22])=[O:21])=[CH:15][CH:14]=2)=[CH:43][CH:44]=1

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 86730094HCID 86730094, compound

Product 1

HCID 71547556HCID 71547556, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

At room temperature, in a 1 L pear-shaped evaporating flask, the compound prepared in Example 8 (24.8 g) was dissolved in a mixed solution of methanol (150 mL) and THF (150 mL) and the solution was stirred. The solution was then heated to 45° C., gradually added with a 1 N sodium hydroxide aqueous solution (107 mL) and stirred overnight at 45° C. The solution was added with a 2 N sodium hydroxide aqueous solution (20 mL). After stirring for 1 hour, the solvent was distilled off under reduced pressure and the solution was further stirred for 1.5 hours at 45° C. A 2 N sodium hydroxide aqueous solution (12 mL) was further added and the solution was stirred for 45 minutes at 55° C. The solution was cooled to 0° C. and added with ice and a 5 N hydrochloric acid aqueous solution until the reaction system was acidic (pH=2). The reaction system was diluted with ethyl acetate and extracted. An organic layer was further washed with a saturated sodium chloride solution and then dried over anhydrous magnesium sulphate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=65:35→44:56→30:70) to give the titled compound (20 g) having the following physical properties.

Workup

  1. stirringstirred overnight at 45° C
  2. stirringAfter stirring for 1 hour
  3. distillationthe solvent was distilled off under reduced pressure
  4. stirringthe solution was further stirred for 1.5 hours at 45° C
  5. additionA 2 N sodium hydroxide aqueous solution (12 mL) was further added
  6. stirringthe solution was stirred for 45 minutes at 55° C
  7. temperatureThe solution was cooled to 0° C.
  8. additionadded with ice
  9. additionThe reaction system was diluted with ethyl acetate
  10. extractionextracted
  11. washAn organic layer was further washed with a saturated sodium chloride solution
  12. dry with materialdried over anhydrous magnesium sulphate
  13. distillationthe solvent was distilled off under reduced pressure
  14. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=65:35→44:56→30:70)

Sources & evidence

ORD record
ord-8b95584cc6bc46b899fdf26b570b9b1c
Source dataset
uspto-grants-2016_05
Patent number
US09340499B2

Reaction notes

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