Hydrochloric Acid → Ethyl 2,2-difluoro-3-hydroxy-3-(4'-propyl-[1,1'-bi(cyclohexane)]-4-yl)propanoate

HRID 80344

반응식

HRID 80344 반응식
Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C1COCC1.[CH2:15]([CH:18]1[CH2:23][CH2:22][CH:21]([CH:24]2[CH2:29][CH2:28][CH:27]([CH:30]=[O:31])[CH2:26][CH2:25]2)[CH2:20][CH2:19]1)[CH2:16][CH3:17].Cl>[Zn].C(OCC)(=O)C>[F:8][C:2]([F:9])([CH:30]([OH:31])[CH:27]1[CH2:26][CH2:25][CH:24]([CH:21]2[CH2:22][CH2:23][CH:18]([CH2:15][CH2:16][CH3:17])[CH2:19][CH2:20]2)[CH2:29][CH2:28]1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2회HCID 69585Ethyl bromodifluoroacetateHCID 109225494'-trans-Propyl-1,1'-bicyclohexyl-4-trans-carboxaldehyde

생성물 1

HCID 68010878Ethyl 2,2-difluoro-3-hydroxy-3-(4'-propyl-[1,1'-bi(cyclohexane)]-4-yl)propanoate수율 54.8%

시약·촉매·용매 2

HCID 23994Zinc촉매HCID 8857Ethyl Acetate용매

실험 절차

To a reaction vessel under a nitrogen atmosphere, 10.7 g of well-dried zinc, 25.0 g of ethyl bromodifluoroacetate (e-14) and 25 ml of THF were added, and the resultant mixture was cooled to 0° C. and stirred for 1 hour. The solution was slowly added dropwise in a temperature range of 20° C. to 25° C. to another reaction vessel under a nitrogen atmosphere in which 19.4 g of 4′-propyl-[1,1′-bi(cyclohexane)]-4-carboaldehyde (e-1) and 100 ml of THF were put, and the resultant mixture was further subjected to heating reflux for 4 hours. After cooling the resultant reaction mixture to 25° C., 300 ml of 1 N HCl aqueous solution and 300 ml of ethyl acetate were added to separate the mixture into an organic layer and an aqueous layer, and an extraction operation was performed. The resultant organic layer was isolated, and washed with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then the resultant solution was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, the resultant residue was purified by a preparative isolation operation by means of column chromatography using a mixed solvent of toluene and ethyl acetate (toluene:ethyl acetate=9:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried, and thus 16.2 g of ethyl 2,2-difluoro-3-hydroxy-3-(4′-propyl-[1,1′-bi(cyclohexane)]-4-yl)propanoate (e-15) was obtained. A yield based on compound (e-1) was 54.8%.

후처리

  1. temperatureto heating
  2. temperaturereflux for 4 hours
  3. temperatureAfter cooling the resultant
  4. customreaction mixture to 25° C.
  5. customto separate the mixture into an organic layer
  6. customThe resultant organic layer was isolated
  7. washwashed with water
  8. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and water, and then the resultant solution was dried over anhydrous magnesium sulfate
  9. distillationThen, the solvent was distilled off under reduced pressure
  10. customthe resultant residue was purified by a preparative isolation operation by means of column chromatography
  11. dry with materialethyl acetate=9:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried

출처 및 근거

ORD 기록
ord-f7124124cd6c4fdc84a96f3eea384351
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846164B2

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