Trimethylsilylacetylene → 1-Ethynyl-3-methoxymethoxymethyl-benzene

HRID 1891970Notes

Reaction equation

HRID 1891970 reaction equation
BrC1C=CC=C(COCOC)C=1.C[Si](C#C)(C)C.C(N(CC)C(C)C)(C)C.[CH3:28][O:29][CH2:30][O:31][CH2:32][C:33]1[CH:34]=[C:35]([C:39]#[C:40][Si](C)(C)C)[CH:36]=[CH:37][CH:38]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1.CN1CCCC1=O>[C:39]([C:35]1[CH:36]=[CH:37][CH:38]=[C:33]([CH2:32][O:31][CH2:30][O:29][CH3:28])[CH:34]=1)#[CH:40]

Participants

10

Reactant 5

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 114475781-Bromo-3-[(methoxymethoxy)methyl]benzene2×HCID 66707789(3-Methoxymethoxymethyl-phenylethynyl)-trimethyl-silane

Product 1

HCID 144816921-Ethynyl-3-methoxymethoxymethyl-benzene

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 1-bromo-3-methoxymethoxymethyl-benzene (3.0 g, 13 mmol) described in Manufacturing Example 214-1-1, trimethylsilylacetylene (2.6 g, 26 mmol), N,N-diisopropylethylamine (3.4 g, 26 mmol), copper (I) iodide (500 mg, 2.6 mmol), and 1-methyl-2-pyrrolidone (30 mL) was added tetrakis(triphenylphosphine)palladium (0) (1.5 g, 1.3 mmol), which was stirred for 15 minutes at 60° C. This mixture was partitioned into ethyl acetate and water. The organic layer was separated and concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=8:1) to obtain a mixture of (3-methoxymethoxymethyl-phenylethynyl)-trimethyl-silane and 1-bromo-3-methoxymethoxymethyl-benzene (3.0 g of mixture, including approximately 30% (3-methoxymethoxymethyl-phenylethynyl)-trimethyl-silane). Tetrabutylammonium fluoride (2 mL, 1 M tetrahydrofuran solution) was added to a tetrahydrofuran (20 mL) solution of this mixture, which was stirred for 15 minutes at room temperature. The reaction solution was partitioned into ethyl acetate and water. The organic layer was separated and concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=20:1) to obtain 1-ethynyl-3-methoxymethoxymethyl-benzene (470 mg). To a methanol (10 mL) solution of this 1-ethynyl-3-methoxymethoxymethyl-benzene (470 mg, 2.6 mmol) was added 5 N hydrochloric acid, which was stirred for 25 minutes at 70° C. The reaction solution was partitioned into ethyl acetate and water. The organic layer was separated and concentrated under a reduced pressure to obtain the title compound (350 mg, 20%).

Workup

  1. customThis mixture was partitioned into ethyl acetate and water
  2. customThe organic layer was separated
  3. concentrationconcentrated under a reduced pressure
  4. customThe residue was purified by silica gel column chromatography (heptane:ethyl acetate=8:1)
  5. customto obtain
  6. stirringwas stirred for 15 minutes at room temperature
  7. customThe reaction solution was partitioned into ethyl acetate and water
  8. customThe organic layer was separated
  9. concentrationconcentrated under a reduced pressure
  10. customThe residue was purified by silica gel column chromatography (heptane:ethyl acetate=20:1)

Sources & evidence

ORD record
ord-96c457147a6f4d47a395edf07562cef3
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

Loading…