Water → HCID 86591709, compound

HRID 480985Notes

Reaction equation

HRID 480985 reaction equation
[OH:1][C:2]1[C:9]([CH3:10])=[C:8]([CH3:11])[C:7]([O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)=[CH:6][C:3]=1[CH:4]=[O:5].Br[CH2:20][C:21]([O:23][CH3:24])=[O:22].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH3:24][O:23][C:21](=[O:22])[CH2:20][O:1][C:2]1[C:3]([CH:4]=[O:5])=[CH:6][C:7]([O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)=[C:8]([CH3:11])[C:9]=1[CH3:10]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 22026141HCID 22026141, compound

Product 1

HCID 86591709HCID 86591709, compoundYield 51.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-hydroxy-3,4-dimethyl-5-(tetrahydro-pyran-2-yloxy)-benzaldehyde (150 mg) from Step 1, methyl bromoacetate (180 mg) and potassium-carbonate (200 mg) in DMF (10 mL) was stirred at room temperature for 2 hours. Then the solution was poured into water and extracted with ethylacetate. The ethyl acetate was washed with water and brine, dried over MgSO4 and concentrated. The residue was purified by silica gel column eluting with hexane and ethyl acetate (9:1) to give 100 mg of [6-formyl-2,3-dimethyl-4-(tetrahydro-pyran-2-yloxy)-phenoxy]-acetic acid methyl ester, which was then dissolved in DMF (15 mL). To this solution was added cesium carbonate (200 mg) and the mixture was stirred at room temperature overnight. Then the solution was poured into water and extracted with ethylacetate. The organic layer was washed with water and brine, dried over MgSO4 and concentrated to give 6,7-dimethyl-5-(tetrahydro-pyran-2-yloxy)-benzofuran-2-carboxylic acid methyl ester. The tetrahydropyranyl ether was dissolved in methanol, p-toluenesulfonic acid monohydrate (20 mg) was added, and the solution was stirred at room temperature for an additional 30 min. After the addition of a small amount of NaHCO3, the methanol was evaporated. The residue was purified by silica gel column chromatography, eluting with hexane and ethyl acetate (7:3) to give 30 mg of 5-hydroxy-6,7-dimethyl-benzofuran-2-carboxylic acid methyl ester. 1H NMR (CDCl3, 300 MHz) δ: 7.39 (s, 1H), 6.87 (s, 1H), 4.75 (s, 1H), 3.95 (s, 3H), 2.50, 2.26 (2s, 6H) ppm.

Workup

  1. extractionextracted with ethylacetate
  2. washThe ethyl acetate was washed with water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column
  6. washeluting with hexane and ethyl acetate (9:1)

Sources & evidence

ORD record
ord-632f4dd65d2940f18717ef06a7e74437
Source dataset
uspto-grants-2003_11
Patent number
US06653346B1

Reaction notes

Loading…