Sodium Hydroxide → Tert-butyl 2-((1-(4-fluorophenyl)cyclohexyl)methoxy)acetate

HRID 71265Notes

Reaction equation

HRID 71265 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:14][OH:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-].[Na+].Br[CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:14][O:15][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 66685762(1-(4-Fluorophenyl)cyclohexyl)methanol

Product 1

HCID 66685225Tert-butyl 2-((1-(4-fluorophenyl)cyclohexyl)methoxy)acetateYield 60%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (1-(4-fluorophenyl)cyclohexyl)methanol (108 mg, 521 μmol) in toluene was cooled to 0° C. and treated with a 50% aq. NaOH solution (500 μL) followed by tetrabutylammonium hydrogen sulfate (44 mg, 130 μmol). The mixture was stirred at 0° C. for 30 min and tert-butyl bromoacetate (152 mg, 781 μmol) was added. The ice bath was removed, and stirring was continued at room temperature for 2 h. The reaction mixture was diluted with EtOAc and water. The organic layer was separated, washed with water, brine, dried (Na2SO4), and concentrated. The crude oil was chromatographed on silica gel (Teledyne-Isco RediSep 12 g silica gel column) and eluted with hexanes, followed by 1% and 3% EtOAc in hexanes to obtain tert-butyl 2-((1-(4-fluorophenyl)cyclohexyl)methoxy)acetate (100 mg, 60% yield) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ ppm 7.28-7.46 (m, 2H), 6.92-7.09 (m, 2H), 3.78 (s, 2H), 3.39 (s, 2H), 2.09 (d, 2H), 1.67-1.86 (m, 2H), 1.47-1.59 (m, 4H), 1.44 (s, 9H), 1.31-1.38 (m, 2H).

Workup

  1. customThe ice bath was removed
  2. stirringstirring
  3. waitwas continued at room temperature for 2 h
  4. additionThe reaction mixture was diluted with EtOAc and water
  5. customThe organic layer was separated
  6. washwashed with water, brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude oil was chromatographed on silica gel (Teledyne-Isco RediSep 12 g silica gel column)
  10. washeluted with hexanes

Sources & evidence

ORD record
ord-38af51702e1f4c52a17acec186030675
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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