Methanol → HCID 84649094, compound

HRID 1849723Notes

Reaction equation

HRID 1849723 reaction equation
O[C:2]1([CH3:13])[CH2:7][CH2:6][CH:5]([C:8](OCC)=[O:9])[CH2:4][CH2:3]1.C(N(S(F)(F)[F:20])CC)C.CO.[BH4-].[Li+]>ClCCl.C(OCC)(=O)C.O1CCCC1>[F:20][C:2]1([CH3:13])[CH2:7][CH2:6][CH:5]([CH2:8][OH:9])[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 887MethanolHCID 123472(Diethylamino)sulfur trifluorideHCID 4148881Lithium borohydrideHCID 21911966Ethyl 4-hydroxy-4-methylcyclohexane-1-carboxylate

Product 1

HCID 84649094HCID 84649094, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 4-hydroxy-4-methylcyclohexanecarboxylate (2.50 g, 13.42 mmol) in dichloromethane (35 mL) at 0° C. was added with diethylaminosulfur trifluoride (14.2 mL, 107.40 mmol) slowly under nitrogen. The resulting mixture was stirred for 24 hours. The reaction mixture was diluted with ethyl acetate (100 mL) and poured into ice (200 g). The organic layer was washed with saturated sodium bicarbonate (3×100 mL) and brine (100 mL); dried with anhydrous sodium sulfate; filtered and concentrated in vacuo to provide the crude product as an oil; which was dissolved in anhydrous tetrahydrofuran (60 mL) and anhydrous methanol (1.10 mL, 26.8 mmol). To the mixture was added lithium borohydride (4 M solution in tetrahydrofuran, 6.70 mL, 26.8 mmol) dropwise and the resulting mixture was refluxed under nitrogen for 4 hours. The reaction mixture was cooled to ambient temperature and quenched with water and then 3 M aqueous hydrochloric acid solution. The mixture was diluted with ethyl acetate (150 mL) and the organic layer was washed with saturated sodium bicarbonate (2×100 mL) and brine (100 mL); dried with anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (2:1 hexanes:ethyl acetate) to provide the title compound as a colorless oil (0.66 g, 34%): 1H NMR (300 MHz, CDCl3) δ 3.50-3.43 (m, 2H), 1.97-1.86 (m, 1H), 1.85-1.71 (m, 2H), 1.69-1.52 (m, 4H), 1.49-1.24 (m, 5H), 1.20-1.03 (m, 1H).

Workup

  1. washThe organic layer was washed with saturated sodium bicarbonate (3×100 mL) and brine (100 mL)
  2. dry with materialdried with anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto provide the crude product as an oil
  6. temperaturethe resulting mixture was refluxed under nitrogen for 4 hours
  7. customquenched with water
  8. additionThe mixture was diluted with ethyl acetate (150 mL)
  9. washthe organic layer was washed with saturated sodium bicarbonate (2×100 mL) and brine (100 mL)
  10. dry with materialdried with anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by silica gel column chromatography (2:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-3e798caf92e6411db7efb89a2248d884
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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