Potassium bis(trimethylsilyl)amide → Ethyl 2-(2,6-bis{[(methyloxy)methyl]oxy}phenyl)-2-propenoate

HRID 1023629Notes

Reaction equation

HRID 1023629 reaction equation
[CH3:1][Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:11][O:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][O:23][CH3:24])[C:16]=1[C:25](=O)[C:26]([O:28][CH2:29][CH3:30])=[O:27]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH3:11][O:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][O:23][CH3:24])[C:16]=1[C:25](=[CH2:1])[C:26]([O:28][CH2:29][CH3:30])=[O:27]

Participants

5

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 67235675Ethyl (2,6-bis{[(methyloxy)methyl]oxy}phenyl)(oxo)acetate2×

Product 1

HCID 67235183Ethyl 2-(2,6-bis{[(methyloxy)methyl]oxy}phenyl)-2-propenoateYield 79.3%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of methyltriphenylphosphonium bromide (3.13 g, 8.75 mmol) in dry tetrahydrofuran (30 ml) at 0° C. KHMDS (1.745 g, 8.75 mmol) was slowly added and the reaction mixture was stirred for 15 minutes at 0° C. and for 45 minutes at room temperature. The reaction mixture was cooled to 0° C. and a solution of ethyl (2,6-bis{[(methyloxy)methyl]oxy}phenyl)(oxo)acetate (Reference Intermediate 209, 1.74 g) in dry tetrahydrofuran (10 mL) was slowly added and the reaction mixture was stirred for 2 hours at 0° C. The reaction was quenched with an aqueous saturated solution of ammonium chloride (10 ml), diluted with water (20 ml) and extracted with ethyl acetate (2×50 ml). The organic layer was dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography (Biotage system) on silica gel using a 100 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 8:2 as eluents affording the title compound as a colourless oil (1.37 g).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringthe reaction mixture was stirred for 2 hours at 0° C
  3. customThe reaction was quenched with an aqueous saturated solution of ammonium chloride (10 ml)
  4. additiondiluted with water (20 ml)
  5. extractionextracted with ethyl acetate (2×50 ml)
  6. dry with materialThe organic layer was dried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash chromatography (Biotage system) on silica gel using a 100 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 8:2 as eluents

Sources & evidence

ORD record
ord-7cec6a699f714496a33324171ce43f3d
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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