Water → 1-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-3-methoxymethyl-3-methyl-pyrrolidine

HRID 2407344Notes

Reaction equation

HRID 2407344 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][N:12]1[CH2:16][CH2:15][C:14]([CH2:18][OH:19])([CH3:17])[CH2:13]1.[H-].[Na+].I[CH3:23].O>O1CCCC1>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][N:12]1[CH2:16][CH2:15][C:14]([CH2:18][O:19][CH3:23])([CH3:17])[CH2:13]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25175667[1-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-3-methyl-pyrrolidin-3-yl]-methanol

Product 1

HCID 251750031-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-3-methoxymethyl-3-methyl-pyrrolidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 56 mg (0.21 mmol) of [1-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-3-methyl-pyrrolidin-3-yl]-methanol in 1.5 ml of tetrahydrofuran was added to a flask containing 58 mg (2.40 mmol) of sodium hydride, previously washed with heptane under argon. The reaction mixture was stirred at 60° C. for 2 h, cooled to 0° C. followed by dropwise addition of a solution containing 16 μl (0.25 mmol) of iodomethane in tetrahydrofuran (0.5 ml). The reaction mixture was allowed to warm to room temperature and the stirring was continued for 1½ h. Water was slowly added and tetrahydrofuran was evaporated off and the water phase was extracted with dichloromethane (3×25 ml). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. Purification by column chromatography (silica gel, ethyl acetate/heptane, 7:13) yielded the desired pure methyl ether.

Workup

  1. washpreviously washed with heptane under argon
  2. temperaturecooled to 0° C.
  3. additionfollowed by dropwise addition of a solution
  4. temperatureto warm to room temperature
  5. waitthe stirring was continued for 1½ h
  6. customtetrahydrofuran was evaporated off
  7. extractionthe water phase was extracted with dichloromethane (3×25 ml)
  8. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customPurification by column chromatography (silica gel, ethyl acetate/heptane, 7:13)

Sources & evidence

ORD record
ord-216d94b86b1f405db9babc2f20e3605f
Source dataset
uspto-grants-2014_08
Patent number
US08809536B2

Reaction notes

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