3,4,5-Trimethoxybenzaldehyde → 5-Ethynyl-1,2,3-trimethoxybenzene

HRID 532979Notes

Reaction equation

HRID 532979 reaction equation
C(Br)(Br)(Br)Br.[CH:6]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([O:37][CH3:38])[C:34]=1[O:35][CH3:36])[CH:30]=O.[Li]CCCC.[NH4+].[Cl-]>C(Cl)Cl.C1COCC1>[C:30]([C:29]1[CH:32]=[C:33]([O:37][CH3:38])[C:34]([O:35][CH3:36])=[C:27]([O:26][CH3:25])[CH:28]=1)#[CH:6]

Participants

8

Reactant 5

HCID 68583,4,5-TrimethoxybenzaldehydeHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 25517Ammonium ChlorideHCID 178418339Butyllithium

Product 1

HCID 118302605-Ethynyl-1,2,3-trimethoxybenzeneYield 79%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a flame-dried 50 mL round-bottom flask was added CBr4 (2.54 g, 7.65 mmol). DCM (20 mL) was added and the solution cooled to 0° C. Ph3P (4.01 g, 15.30 mmol) was added and the solution stirred at 0° C. for 15 min. 3,4,5-Trimethoxybenzaldehyde (1.0 g, 5.10 mmol) in DCM (6.0 mL) was added dropwise. The solution was stirred at 0° C. for 5 min. The solvent was removed under reduced pressure, and the resulting oil was filtered through a plug of silica and washed with Hex:EtOAc (9:1, 500 mL; 4:1, 500 mL). The combined organics were concentrated to give the crude dibromo-olefin (2.31 g, 128%), which was dissolved in THF (60 mL) and cooled to −78° C. n-BuLi (13.1 mL, 19.68 mmol, 1.5 M) was added dropwise and the solution stirred at −78° C. for 30 min. Saturated NH4Cl (10 mL) was added and the solution warmed to room temperature. The layers were separated, and the organics were washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography (SiO2, 80 g) using 10% EtOAc in hexanes as the eluent to afford 5-Ethynyl-1,2,3-trimethoxybenzene as a colorless oil (0.770 g, 79%): Rf=0.30 (4:1, Hex:EtOAc); 1H NMR (CDCl3) δ 6.71 (s, 2H), 3.84 (s, 3H), 3.83 (s, 6H), 3.03 (s, 1H); 13C NMR (CDCl3) δ 153.1, 117.1, 109.4, 103.3, 83.8, 76.4, 61.0, 56.2, 56.1; HRFAB [M+Li] 199.0952 (calculated C11H12O3Li: 199.0946).

Workup

  1. stirringThe solution was stirred at 0° C. for 5 min
  2. customThe solvent was removed under reduced pressure
  3. filtrationthe resulting oil was filtered through a plug of silica
  4. washwashed with Hex
  5. concentrationThe combined organics were concentrated
  6. customto give the crude dibromo-olefin (2.31 g, 128%), which
  7. additionwas added dropwise
  8. stirringthe solution stirred at −78° C. for 30 min
  9. temperaturethe solution warmed to room temperature
  10. customThe layers were separated
  11. washthe organics were washed with brine (10 mL)
  12. dry with materialdried over anhydrous Na2SO4
  13. concentrationconcentrated
  14. customThe residue was purified by flash chromatography (SiO2, 80 g)

Sources & evidence

ORD record
ord-5d95d881502a4005aa1a8cf5a5fd1a0b
Source dataset
uspto-grants-2014_10
Patent number
US08853228B2

Reaction notes

Loading…