Chloromethyl Methyl Ether → 7,8-Difluoro-6-methoxymethoxy-2-pentylchroman

HRID 2244839Notes

Reaction equation

HRID 2244839 reaction equation
[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[O:9]2)=[CH:4][C:3]=1[OH:18].C(N(C(C)C)C(C)C)C.[CH3:28][O:29][CH2:30]Cl.C(N(CC)CC)C>ClCCl.O>[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[O:9]2)=[CH:4][C:3]=1[O:18][CH2:28][O:29][CH3:30]

Participants

7

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 46834772HCID 46834772, compound

Product 1

HCID 592152597,8-Difluoro-6-methoxymethoxy-2-pentylchroman

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

16.9 g (65.9 mmol) of 7,8-difluoro-2-pentylchroman-6-ol are dissolved in 110 ml of dichloromethane, and 13.5 ml (77.1 mmol) of N-ethyldiisopropylamine are added with ice-cooling. After 5 min, 6.0 ml (79.0 mmol) of chloromethyl methyl ether are metered in the temperature range from 15 to 30° C. After 16 h at room temperature, 50 ml of triethylamine are added, and the batch is stirred again for 24 h. Water is added to the reaction mixture, and the organic phase is separated off. The aqueous phase is extracted with dichloromethane, and the combined organic phases are washed successively with water and sat. sodium chloride soln. The solution is dried using sodium sulfate and concentrated to dryness. The crude product is purified by column chromatography (SiO2, 1-chlorobutane), giving 7,8-difluoro-6-methoxymethoxy-2-pentylchroman as a yellowish oil.

Workup

  1. temperaturecooling
  2. customare metered in the temperature range from 15 to 30° C
  3. waitAfter 16 h at room temperature
  4. customthe organic phase is separated off
  5. extractionThe aqueous phase is extracted with dichloromethane
  6. washthe combined organic phases are washed successively with water and sat. sodium chloride soln
  7. customThe solution is dried
  8. concentrationconcentrated to dryness
  9. customThe crude product is purified by column chromatography (SiO2, 1-chlorobutane)

Sources & evidence

ORD record
ord-d2684f28c73b43cbb22370c06e970e2d
Source dataset
uspto-grants-2010_03
Patent number
US07678929B2

Reaction notes

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