Hydrochloric Acid → 2-Fluoro-3-(4-propylcyclohexyl)propan-1-ol

HRID 80343Notes

Reaction equation

HRID 80343 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][CH:8]([CH2:14][CH:15]1[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][CH3:23])[CH2:17][CH2:16]1)[C:9](OCC)=[O:10].Cl.C(OCC)(=O)C>C1COCC1>[F:7][CH:8]([CH2:14][CH:15]1[CH2:16][CH2:17][CH:18]([CH2:21][CH2:22][CH3:23])[CH2:19][CH2:20]1)[CH2:9][OH:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 86684974Ethyl 2-fluoro-3-(4-propylcyclohexyl)propanoate

Product 1

HCID 680108502-Fluoro-3-(4-propylcyclohexyl)propan-1-olYield 74.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a reaction vessel under a nitrogen atmosphere, 0.3 g of lithium aluminum hydride and 10 ml of THF were added, and the resultant mixture was cooled to −10° C. Thereto, 1.1 g of ethyl 2-fluoro-3-(4-propylcyclohexyl)propanoate (e-11) dissolved in 10 ml of THF was added dropwise in a temperature range of −10° C. to 0° C. Then, the resultant mixture was heated to 25° C., and stirred for 1 hour. Subsequently, 100 ml of 1 N HCl aqueous solution and 100 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, and then the resultant solution was dried over anhydrous magnesium sulfate. The resultant solution was concentrated 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=5:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried, and thus 0.68 g of 2-fluoro-3-(4-propylcyclohexyl)propan-1-ol (e-12) was obtained. A yield based on compound (e-11) was 75.7%.

Workup

  1. additionwas added dropwise in a temperature range of −10° C. to 0° C
  2. customto separate the mixture into an organic layer
  3. customThe resultant organic layer was isolated
  4. washwashed with water
  5. dry with materialthe resultant solution was dried over anhydrous magnesium sulfate
  6. concentrationThe resultant solution was concentrated under reduced pressure
  7. customthe resultant residue was purified by a preparative isolation operation by means of column chromatography
  8. dry with materialethyl acetate=5:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried

Sources & evidence

ORD record
ord-3c8d0865f01a4b4ca5550c633903633b
Source dataset
uspto-grants-2014_09
Patent number
US08846164B2

Reaction notes

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