Chloromethyl Methyl Ether → 5-Bromo-2-[(methoxymethoxy)methyl]-2,4,6,7-tetramethyl-2,3-dihydro-1-benzofuran

HRID 1850423Notes

Reaction equation

HRID 1850423 reaction equation
C(N(C(C)C)C(C)C)C.Cl[CH2:11][O:12][CH3:13].[Br:14][C:15]1[C:16]([CH3:29])=[C:17]([CH3:28])[C:18]2[O:22][C:21]([CH2:24][OH:25])([CH3:23])[CH2:20][C:19]=2[C:26]=1[CH3:27].O.C(=O)(O)[O-].[Na+]>C1COCC1>[Br:14][C:15]1[C:16]([CH3:29])=[C:17]([CH3:28])[C:18]2[O:22][C:21]([CH2:24][O:25][CH2:11][O:12][CH3:13])([CH3:23])[CH2:20][C:19]=2[C:26]=1[CH3:27]

Participants

6

Reactant 4

HCID 7864Chloromethyl Methyl Ether2×HCID 81531Diisopropylethylamine2×HCID 66759014(5-Bromo-2,4,6,7-tetramethyl-2,3-dihydro-1-benzofuran-2-yl)methanolHCID 86585896Sodium bicarbonate water

Product 1

HCID 667606425-Bromo-2-[(methoxymethoxy)methyl]-2,4,6,7-tetramethyl-2,3-dihydro-1-benzofuranYield 75.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyldiisopropylamine (1.26 g, 9.74 mmol) and chloromethylmethylether (627 mg, 7.79 mmol) were serially added to a solution of THF (15 mL) containing (5-bromo-2,4,6,7-tetramethyl-2,3-dihydro-1-benzofuran-2-yl)methanol (1.85 g, 6.49 mmol) synthesized in Reference Example 123 under ice-cooling condition, and the mixture was warmed to room temperature and stirred for 15 hours. Ethyldiisopropylamine (1.26 g, 9.74 mmol) and chloromethylmethylether (523 mg, 6.49 mmol) were further added serially to the reaction solution under ice-cooling condition, and the mixture was warmed to room temperature and stirred for 15 hours. The reaction solution was poured into saturated sodium bicarbonate water, and THF was removed under reduced pressure, followed by extraction using ethyl acetate. The extract was washed with saturated saline and dried using anhydrous magnesium sulfate. After that, the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate 96:4-80:20) to give 1.62 g of the title compound as an oily product (yield: 76%).

Workup

  1. customsynthesized in Reference Example 123 under ice-
  2. temperaturecooling condition
  3. temperaturecooling condition
  4. temperaturethe mixture was warmed to room temperature
  5. stirringstirred for 15 hours
  6. customwas removed under reduced pressure
  7. extractionfollowed by extraction
  8. washThe extract was washed with saturated saline
  9. customdried
  10. customAfter that, the solvent was removed under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate 96:4-80:20)

Sources & evidence

ORD record
ord-f8b6d15f46374bbe88bd1a4a58be860d
Source dataset
uspto-grants-2015_02
Patent number
US08957069B2

Reaction notes

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