Methyl iodide → Ethyl 2-fluoro-3-(((methylthio)carbonothioyl)oxy)-3-(4-propylcyclohexyl)propanoate

HRID 80341Notes

Reaction equation

HRID 80341 reaction equation
[F:1][CH:2]([CH:8]([OH:18])[CH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][CH3:17])[CH2:11][CH2:10]1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].C1CCN2C(=NCCC2)CC1.[C:30](=[S:32])=[S:31].[CH3:33]I>C(OCC)(=O)C.O.CN(C=O)C>[F:1][CH:2]([CH:8]([O:18][C:30]([S:32][CH3:33])=[S:31])[CH:9]1[CH2:10][CH2:11][CH:12]([CH2:15][CH2:16][CH3:17])[CH2:13][CH2:14]1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86684972Ethyl 2-fluoro-3-hydroxy-3-(4-propylcyclohexyl)propanoate

Product 1

HCID 86684973Ethyl 2-fluoro-3-(((methylthio)carbonothioyl)oxy)-3-(4-propylcyclohexyl)propanoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a reaction vessel under a nitrogen atmosphere, 3.8 g of ethyl 2-fluoro-3-hydroxy-3-(4-propylcyclohexyl)propanoate (e-9), 8.9 g of DBU, 8.7 ml of carbon disulfide and 40 ml of DMF were added, and the resultant mixture was stirred at 25° C. for 1.5 hours. Subsequently, 20.5 g of methyl iodide was added to a reaction mixture, and the resultant mixture was stirred at 25° C. for 1.5 hours. Then, 100 ml of water 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, an aqueous solution of sodium thiosulfate, and 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 heptane and ethyl acetate (heptane:ethyl acetate=9:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried, and thus 2.1 g of ethyl 2-fluoro-3-(((methylthio)carbonothioyl)oxy)-3-(4-propylcyclohexyl)propanoate (e-10) was obtained. A yield based on compound (e-8) was 46.3%.

Workup

  1. customto separate the mixture into an organic layer
  2. customThe resultant organic layer was isolated
  3. washwashed with water
  4. dry with materialan aqueous solution of sodium thiosulfate, and water, and then the resultant solution was dried over anhydrous magnesium sulfate
  5. concentrationThe resultant solution was concentrated under reduced pressure
  6. customthe resultant residue was purified by a preparative isolation operation by means of column chromatography
  7. dry with materialethyl acetate=9:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried

Sources & evidence

ORD record
ord-685aa2b849454b6d9c5405c0731a5a46
Source dataset
uspto-grants-2014_09
Patent number
US08846164B2

Reaction notes

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