Ethyl bromoacetate → 2-(Carboethoxy)methyl-5,6-dimethoxy-3-phenyl-1,2,3,4-tetrahydronaph-thalen-1-one

HRID 54135Notes

Reaction equation

HRID 54135 reaction equation
[CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH:6]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:7][C:8]2=[O:15].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35]>C1COCC1>[C:34]([CH2:33][CH:7]1[CH:6]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:5][C:4]2[C:9](=[CH:10][CH:11]=[C:12]([O:13][CH3:14])[C:3]=2[O:2][CH3:1])[C:8]1=[O:15])([O:36][CH2:37][CH3:38])=[O:35]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 124785445,6-Dimethoxy-3-phenyl-3,4-dihydronaphthalen-1(2H)-one

Product 1

HCID 199611482-(Carboethoxy)methyl-5,6-dimethoxy-3-phenyl-1,2,3,4-tetrahydronaph-thalen-1-oneYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5,6-dimethoxy-3-phenyl-1,2,3,4-tetrahydronaphthalen-1-one (5 g, 17.7 mmol, 1.0 equivalents), the product of Example 1, in 150 mL of dry THF cooled to -78° C., was added 19.5 mL of lithium bis(trimethylsilyl)amide (1M solution in THF, 19.5 mmol, 1.1 equivalent). The resultant solution was stirred at -78° C. for 1 h and then ethyl bromoacetate (2.2 mL, 19.5 mmol, 1.1 equivalent) was added in one portion. The reaction solution was then allowed to warm to ambient temperature and was stirred for 3 h. The reaction was quenched by the addition of 50 mL of saturated ammonium chloride solution. The resultant light yellow colored THF layer was separated and evaporated to an oil. The oil was taken up into 200 mL of methylene chloride and the methylene chloride solution was washed with 2×50 mL of water and 50 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluted with ethyl acetate/hexane (1:6) to give 5.4 g (83% yield) of the title compound as a white solid; 1H NMR (CDCl3) δ: 1.2 (t, 3H, J=7.5 Hz), 2.45 (m, 2H), 3.03 (m, 1H), 3.30 (m, 2H), 3.43 (m, 1H), 3.78 (s, 3H), 3.93 (s, 3H), 4.07 (m, 2H), 6.92 (d, 1H, J=9.0 Hz), 7.32 (m, 5H), 7.89 (d, 1H, J=9.0 Hz). Analysis calculated for C22H24O5 : C, 71.72; H, 6.57. Found: C, 71.39; H, 6.63.

Workup

  1. customThe reaction was quenched by the addition of 50 mL of saturated ammonium chloride solution
  2. customThe resultant light yellow colored THF layer was separated
  3. customevaporated to an oil
  4. washthe methylene chloride solution was washed with 2×50 mL of water and 50 mL of brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed on silica gel
  9. washeluted with ethyl acetate/hexane (1:6)

Sources & evidence

ORD record
ord-87814d385d10485f96259238ecff7f07
Source dataset
uspto-grants-1997_04
Patent number
US05621133

Reaction notes

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