Ethyl bromoacetate → [6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-yl]-acetic acid ethyl ester

HRID 2404202Notes

Reaction equation

HRID 2404202 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH:13]3[CH2:18][CH2:17][CH:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]3)[CH:8]=2)[CH:3]=1.C([Li])CCC.CCCCCC.Br[CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37]>CCOCC>[CH2:39]([O:38][C:36](=[O:37])[CH2:35][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH:13]3[CH2:18][CH2:17][CH:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]3)[CH:8]=2)[CH:3]=1)[CH3:40]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 8058HexaneHCID 509863542-Bromo-6-(4-tert-butyl-cyclohexyloxy)-naphthaleneHCID 178418339Butyllithium

Product 1

HCID 66926519[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-yl]-acetic acid ethyl esterYield 22.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-bromo-6-(4-tert-butyl-cyclohexyloxy)-naphthalene (2 g, 5.5 mmol) in ether (10 mL) under nitrogen was added 1.6 M n-butyllithium in hexane (4 mL, 6.4 mmol) at 0° C. The solution was stirred for 30 min at 0° C., then treated with copper(I) bromide-dimethyl sulfide complex (0.8 g, 3.9 mmol). After 2 hrs stirring, a solution of ethyl bromoacetate (0.7 mL, 6 mmol) in ether (4 mL) was added. The solution was stirred at 0° C. for 2 hrs, then warmed to room temperature for 3 hrs. The reaction was quenched with 10% HCl aqueous then the insoluble was filtered off. The organic layer was washed with water, sodium bicarbonate aqueous, dried over MgSO4, filtered and concentrated. The crude was purified via silica gel column eluted with EtOAc in hexanes from 0 to 10% to give light yellow solid (0.45 g, yield: 22% yield). ESI-MS: 369.20 (M+H)+.

Workup

  1. additiontreated with copper(I) bromide-dimethyl sulfide complex (0.8 g, 3.9 mmol)
  2. stirringAfter 2 hrs stirring
  3. stirringThe solution was stirred at 0° C. for 2 hrs
  4. temperaturewarmed to room temperature for 3 hrs
  5. customThe reaction was quenched with 10% HCl aqueous
  6. filtrationthe insoluble was filtered off
  7. washThe organic layer was washed with water, sodium bicarbonate aqueous
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude was purified via silica gel column
  12. washeluted with EtOAc in hexanes from 0 to 10%

Sources & evidence

ORD record
ord-70394fa315cc47759e0723186e743d2c
Source dataset
uspto-grants-2014_08
Patent number
US08802659B2

Reaction notes

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