Sodium Carbonate → 1-Methyl-5-nitro-4-propoxy-2-vinyl-benzene

HRID 386777Notes

Reaction equation

HRID 386777 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]([CH3:11])C)[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][C:3]=1[CH3:15].[CH2:16](OB(C=C)OCCCC)[CH2:17]CC.[C:29](=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O>[CH3:15][C:3]1[CH:4]=[C:5]([N+:12]([O-:14])=[O:13])[C:6]([O:8][CH2:9][CH2:11][CH3:29])=[CH:7][C:2]=1[CH:16]=[CH2:17]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 236543Dibutyl Vinylboronate (stabilized with Phenothiazine)HCID 457903241-Chloro-5-isopropoxy-2-methyl-4-nitrobenzene2×

Product 1

HCID 670710261-Methyl-5-nitro-4-propoxy-2-vinyl-benzene

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 1-chloro-2-methyl-4-nitro-5-isopropoxy-benzene (Intermediate 4, 870 mg, 3.77 mmol), vinylboronic acid dibutyl ester (1.24 mL, 5.6 mmol), and sodium carbonate (2.8 g, 26.4 mmol) in THF/H2O (20/5 mL) is added dichlorobis(triphenylphospine) palladium (II) (132 mg, 5% mmol). The reaction tube is sealed, the mixture is purged with N2 for 3 min and then heated at 90° C. under N2 for overnight. The reaction is cooled to room temperature and poured into saturated aqueous ammonia chloride solution. The crude reaction mixture is extracted with ethyl acetate (3×100 mL). The organic extracts are combined, washed with brine and concentrated. The crude product is purified with silica gel column chromatography (10% ethyl acetate in hexanes) to afford 1-methyl-5-nitro-4-propoxy-2-vinyl-benzene as a yellow solid. 1-Methyl-5-nitro-4-propoxy-2-vinyl-benzene obtained from the previous step (360 mg, 1.63 mmol) is dissolved in DCM (20 mL) and is cooled to −78° C. O3 (g) is bubbled into the solution until the solution's color turns blue/gray. The solution is then purged with N2 (g) until the blue color disappears. The solution is warmed to room temperature and treated with triphenylphospine resin (2 g) pre-swelled in DCM (30 mL). After 30 min, the mixture is filtered, and the filtrate is concentrated to afford 2-methyl-4-nitro-5-propoxy-benzaldehyde as yellow solid.

Workup

  1. customThe reaction tube is sealed
  2. customthe mixture is purged with N2 for 3 min
  3. temperatureThe reaction is cooled to room temperature
  4. additionpoured into saturated aqueous ammonia chloride solution
  5. customThe crude reaction mixture
  6. extractionis extracted with ethyl acetate (3×100 mL)
  7. washwashed with brine
  8. concentrationconcentrated
  9. customThe crude product is purified with silica gel column chromatography (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f955a502828d408d9d9f76c8a8c15e73
Source dataset
uspto-grants-2013_02
Patent number
US08372858B2

Reaction notes

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