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

HRID 714263Notes

Reaction equation

HRID 714263 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-c5b213a40bde4934b2b7452a6557ba37
Source dataset
uspto-grants-2015_11
Patent number
US09187437B2

Reaction notes

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