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

HRID 1506293Notes

Reaction equation

HRID 1506293 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

Procedure

A solution of (1-(4-fluorophenyl)cyclohexyl)methanol (Intermediate I-10A, 108.5 mg, 0.52 mmol) in toluene 91 mL) was cooled to 0° C. A 5N aq. sodium hydroxide solution (500 μL) was added followed by tetra-n-butyl ammonium hydrogen sulfate (44 mg, 0.13 mmol) and stirring was continued for 30 min at 0° C. Tert-butyl bromoacetate (152 mg, 0.78 mmol) was added, the ice bath was removed, and stirring was continued for 2 hrs. The reaction mixture was diluted with ethyl acetate and water. The organic extract was separated, washed with water and brine, dried over sodium sulfate and concentrated in vacuo to obtain a colorless oil, which was purified by flash chromatography on silica gel (Teledyne-Isco REDISEP® 12 g silica gel column). Elution with hexanes (50 mL), followed by 1% and 3% EtOAc in hexanes (100 mL each) afforded tert-butyl 2-((1-(4-fluorophenyl)cyclohexyl)methoxy)acetate (100 mg, 60% yield) as a viscous oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.28-7.46 (2H, m), 6.92-7.09 (2H, m), 3.78 (2H, s), 3.39 (2H, s), 2.09 (2H, d, J=15.31 Hz), 1.67-1.86 (2H, m), 1.47-1.59 (4H, m), 1.44 (9H, s), 1.31-1.38 (2H, m).

Workup

  1. customthe ice bath was removed
  2. stirringstirring
  3. waitwas continued for 2 hrs
  4. additionThe reaction mixture was diluted with ethyl acetate and water
  5. extractionThe organic extract
  6. customwas separated
  7. washwashed with water and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customto obtain a colorless oil, which
  11. customwas purified by flash chromatography on silica gel (Teledyne-Isco REDISEP® 12 g silica gel column)
  12. washElution with hexanes (50 mL)

Sources & evidence

ORD record
ord-6e2946eba512426988206f0bedca080a
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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