Methyl iodide → (3R)-3-(Methoxymethyl)-4-(phenylmethyl)morpholine

HRID 584231Notes

Reaction equation

HRID 584231 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C@H:9]1[CH2:14][OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:18]I>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C@H:9]1[CH2:14][O:15][CH3:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 1514271(r)-(4-benzylmorpholin-3-yl)methanol

Product 1

HCID 54360669(3R)-3-(Methoxymethyl)-4-(phenylmethyl)morpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

A solution of (3R)-4-benzyl-3-hydroxymethylmorpholine (0.94 g) in tetrahydrofuran (10 ml) was added dropwise to a suspension of sodium hydride (60% oil suspension, 0.22 g) in tetrahydrofuran (20 ml) at room temperature under nitrogen atmosphere and the whole was stirred at 70° C. for 1 hour. After cooling, methyl iodide (0.31 ml) was added thereto and the mixture was stirred at 40° C. for 1 hour. After cooling, the mixture was poured into ice water, and extracted with ethyl acetate. The extract was dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane (3:7) as an eluent to give (3R)-4-benzyl-3-methoxymethylmorpholine (0.88 g) as an oil.

Workup

  1. temperatureAfter cooling
  2. stirringthe mixture was stirred at 40° C. for 1 hour
  3. temperatureAfter cooling
  4. extractionextracted with ethyl acetate
  5. dry with materialThe extract was dried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane (3:7) as an eluent

Sources & evidence

ORD record
ord-e0c454a7fffd43649050f8d2af94c3a9
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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