Lithium borohydride → (4-Cyclopentyl-3-(trifluoromethyl)phenyl)methanol

HRID 707757Notes

Reaction equation

HRID 707757 reaction equation
[CH:1]1([C:6]2[CH:15]=[CH:14][C:9]([C:10](OC)=[O:11])=[CH:8][C:7]=2[C:16]([F:19])([F:18])[F:17])[CH2:5][CH2:4][CH2:3][CH2:2]1.[BH4-].[Li+]>O1CCOCC1>[CH:1]1([C:6]2[CH:15]=[CH:14][C:9]([CH2:10][OH:11])=[CH:8][C:7]=2[C:16]([F:17])([F:18])[F:19])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 11097668Methyl 4-cyclopentyl-3-(trifluoromethyl)benzoate

Product 1

HCID 58020942(4-Cyclopentyl-3-(trifluoromethyl)phenyl)methanolYield 16.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of methyl 4-cyclopentyl-3-(trifluoromethyl)benzoate (8.16 g, 30.0 mmol) in 1,4-dioxane (200 mL) was added lithium borohydride solution (2 M in tetrahydrofuran, 30.0 mL, 59.9 mmol). The mixture was heated under reflux for 2.5 h. The mixture was allowed to cool to room temperature and carefully quenched with 1N aqueous HCl solution to pH 5. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatograhy to give the title compound as a colorless oil (1.21 g). 1H NMR (400 MHz, CDCl3) δ ppm 1.56-1.63 (m, 2H), 1.66-1.77 (m, 2H), 1.81-1.91 (m, 2H), 2.03-2.15 (m, 2H), 3.37 (quintet, J=8.00 Hz, 1H), 4.71 (d, J=4.29 Hz, 2H), 7.45-7.47 (m, 1H), 7.49 (d, J=1.14 Hz, 1H), 7.60 (s, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 2.5 h
  3. customcarefully quenched with 1N aqueous HCl solution to pH 5
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. custompurified by silica gel column chromatograhy

Sources & evidence

ORD record
ord-8249338cb1094bba9eb53c280c7cecf0
Source dataset
uspto-grants-2015_11
Patent number
US09175320B2

Reaction notes

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