Hydrochloric Acid → 3-Ethynylbenzenemethanol

HRID 78265Notes

Reaction equation

HRID 78265 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][O:10]COC)[CH:4]=1)#[CH:2].Cl>CO>[C:1]([C:3]1[CH:4]=[C:5]([CH2:9][OH:10])[CH:6]=[CH:7][CH:8]=1)#[CH:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 144816921-Ethynyl-3-methoxymethoxymethyl-benzene

Product 1

HCID 154687703-EthynylbenzenemethanolYield 101.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °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. customThe reaction solution was partitioned into ethyl acetate and water
  2. customThe organic layer was separated
  3. concentrationconcentrated under a reduced pressure

Sources & evidence

ORD record
ord-c10814ec4088405fb114861f1cad8e3c
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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