Diethyl chlorophosphate → 6-Ethynyl-8-trimethylsilanylethynyl-2,2,4,4-tetramethyl chroman

HRID 898669Notes

Reaction equation

HRID 898669 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([C:14]#[C:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:13]=1)[O:10][C:9]([CH3:21])([CH3:20])[CH2:8][C:7]2([CH3:23])[CH3:22])(=O)[CH3:2].C([N-]C(C)C)(C)C.[Li+].P(Cl)(OCC)(OCC)=O>O1CCCC1>[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([C:14]#[C:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:13]=1)[O:10][C:9]([CH3:21])([CH3:20])[CH2:8][C:7]2([CH3:23])[CH3:22])#[CH:2]

Participants

5

Reactant 3

HCID 13139Diethyl chlorophosphateHCID 2724682Lithium diisopropylamide2×HCID 60083892HCID 60083892, compound2×

Product 1

HCID 600838886-Ethynyl-8-trimethylsilanylethynyl-2,2,4,4-tetramethyl chromanYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-acetyl-8-trimethylsilanylethynyl-2,2,4,4-tetramethyl chroman (Compound 36, 0.616 g, 1.88 mmol) in anhydrous tetrahydrofuran (3 mL) was cannulated into a stirred, cooled (−78° C.) solution of lithium diisopropyl amide [2.82 mmol in 2 mL of tetrahydrofuran generated from N,N-diisopropyl amine (0.4 mL, 2.82 mmol) and 1.6M solution of n-butyl lithium in hexanes (1.88 mL, 3 mmol)] and the resulting reaction mixture was stirred at the same temperature for 50 min. Diethyl chlorophosphate (0.35 mL, 2.44 mol) was then added and the reaction mixture was allowed to warm to 0° C. over 1.5 h. The reaction mixture was then cannulated into a stirred, cooled (−78° C.) solution of lithium diisopropyl amide [8.46 mmol in 3 mL of tetrahydrofuran generated from N,N-diisopropyl amine (1.2 mL, 8.46 mmol) and 1.6M solution of n-butyl lithium in hexanes (5.64 mL, 9 mmol)]. The reaction mixture was allowed to warm to −30° C. over 2 h. It was then quenched with water and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue that was subjected to flash column chromatography over silica gel (230-400 mesh) using 1-2.5% ethyl acetate in hexane as the eluent to afford the title compound as a white solid (0.29 g, 50%).

Workup

  1. customthe resulting reaction mixture
  2. temperatureto warm to −30° C. over 2 h
  3. customIt was then quenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo to a residue that

Sources & evidence

ORD record
ord-7d3e33916764497a9fc8c2dbfbc189f8
Source dataset
uspto-grants-2008_04
Patent number
US07351737B2

Reaction notes

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