Chloromethyl Methyl Ether → 7,8-Difluoro-6-methoxymethoxychroman

HRID 2244830Notes

Reaction equation

HRID 2244830 reaction equation
[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][O:9]2)=[CH:4][C:3]=1[OH:13].C(N(C(C)C)C(C)C)C.[CH3:23][O:24][CH2:25]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][CH2:8][O:9]2)=[CH:4][C:3]=1[O:13][CH2:23][O:24][CH3:25]

Participants

7

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 592152417,8-Difluorochroman-6-ol

Product 1

HCID 592152587,8-Difluoro-6-methoxymethoxychroman

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

15.0 g (80.6 mmol) of 7,8-difluorochroman-6-ol are dissolved in 135 ml of dichloromethane, and 16.5 ml (94.2 mmol) of N-ethyldiisopropylamine are added with ice-cooling. After 5 min, 7.34 ml (97.0 mmol) of chloromethyl methyl ether are metered in the temperature range from 15 to 30° C. After 18 h at 20° C., 50 ml of triethylamine are added, and the batch is stirred again for 18 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, n-heptane:MTBE=2:1), giving 7,8-difluoro-6-methoxymethoxychroman as a yellowish solid.

Workup

  1. temperaturecooling
  2. customare metered in the temperature range from 15 to 30° C
  3. waitAfter 18 h at 20° C.
  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, n-heptane:MTBE=2:1)

Sources & evidence

ORD record
ord-85681d7a6e1d4957b3d513ddb39ede20
Source dataset
uspto-grants-2010_03
Patent number
US07678929B2

Reaction notes

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