Hydrochloric Acid → HCID 68452714, compound

HRID 658108Notes

Reaction equation

HRID 658108 reaction equation
C(NC(C)C)(C)C.[C:8]([C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)(=[O:10])[CH3:9].[CH3:17][C:18]1([CH3:32])[O:22][C@H:21]([C:23]2[C:24]([F:31])=[C:25]([CH:28]=[CH:29][CH:30]=2)[CH:26]=[O:27])[CH2:20][O:19]1.Cl>C1COCC1>[CH3:17][C:18]1([CH3:32])[O:22][C@H:21]([C:23]2[C:24]([F:31])=[C:25]([CH:26]([OH:27])[CH2:9][C:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[O:10])[CH:28]=[CH:29][CH:30]=2)[CH2:20][O:19]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 95893-AcetylpyridineHCID 86626219HCID 86626219, compound

Product 1

HCID 68452714HCID 68452714, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

In a stream of argon, anhydrous THF solution containing 0.72 ml of N,N-diisopropylamine was cooled to about −70° C., 3.3 ml of 1.54 M n-butyl lithium-hexane solution was added dropwise thereto, and then the reaction liquid was risen to about −15° C. The reaction liquid was again cooled to about −70° C., mixed with 0.54 ml of 3-acetylpyridine and then stirred at the same temperature for about 30 minutes, and subsequently, 5 ml of anhydrous THF solution containing 1.1 g of 3-((4R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluorobenzaldehyde was gradually added dropwise thereto. After stirring at −70° C. for about 20 minutes and then at about −30° C. for about 3 hours, this was mixed with an appropriate amount of 0.2 M hydrochloric acid aqueous solution and subjected to several times of extraction operation with ethyl acetate. The organic layer was washed with saturated brine and dried with anhydrous magnesium sulfate, and then the solvent was evaporated and the thus formed residue was isolated and purified by a silica gel column chromatography to obtain 0.77 g (45%) of 3-[3-((4R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluorophenyl]-3-hydroxy-1-pyridin-3-yl-propan-1-one as a colorless oil from an ethyl acetate-hexane (7:3) eluate. FA: 346

Workup

  1. addition3.3 ml of 1.54 M n-butyl lithium-hexane solution was added dropwise
  2. customthe reaction liquid
  3. customwas risen to about −15° C
  4. customThe reaction liquid
  5. temperaturewas again cooled to about −70° C.
  6. additionwas gradually added dropwise
  7. stirringAfter stirring at −70° C. for about 20 minutes
  8. waitat about −30° C. for about 3 hours
  9. extractionsubjected to several times of extraction operation with ethyl acetate
  10. washThe organic layer was washed with saturated brine
  11. dry with materialdried with anhydrous magnesium sulfate
  12. customthe solvent was evaporated
  13. customthe thus formed residue was isolated
  14. custompurified by a silica gel column chromatography

Sources & evidence

ORD record
ord-3fa59cdf643141a7b77f5b6a53fbf045
Source dataset
uspto-grants-2011_12
Patent number
US08076367B2

Reaction notes

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