Chlorotrimethylsilane → (5R)-4-(4-methoxybenzyl)-5-methylmorpholine

HRID 1045668Notes

Reaction equation

HRID 1045668 reaction equation
Cl[Si](C)(C)C.[BH4-].[Li+].[CH3:8][O:9][C:10]1[CH:24]=[CH:23][C:13]([CH2:14][N:15]2[C@H:20]([CH3:21])[CH2:19][O:18][CH2:17][C:16]2=O)=[CH:12][CH:11]=1.[OH-].[K+]>O1CCCC1.CO>[CH3:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][N:15]2[C@H:20]([CH3:21])[CH2:19][O:18][CH2:17][CH2:16]2)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 14797Potassium HydroxideHCID 4148881Lithium borohydrideHCID 60073921(5R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one

Product 1

HCID 57870144(5R)-4-(4-methoxybenzyl)-5-methylmorpholineYield 96.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Chlorotrimethylsilane (37 g, 341 mmol) was added to a solution of lithium borohydride (3.7 g, 170 mmol) in tetrahydrofuran (200 ml) and the mixture was stirred for one hour at room temperature. A solution of (5R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one (19.6 g, 83.3 mmol) in tetrahydrofuran (20 ml) was added to the solution and the mixture was stirred for one hour at room temperature. After careful addition of methanol with ice-cooled solution, pH was adjusted to 12-14 with 6N aqueous potassium hydroxide and the solution was stirred for 2 hours at 80° C. After cooling, the solution was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform) to afford (5R)-4-(4-methoxybenzyl)-5-methylmorpholine (17.8 g, 80.3 mmol, 96%) as colorless oil.

Workup

  1. stirringthe mixture was stirred for one hour at room temperature
  2. temperaturecooled solution, pH
  3. stirringthe solution was stirred for 2 hours at 80° C
  4. temperatureAfter cooling
  5. customthe solution was partitioned between water and ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform)

Sources & evidence

ORD record
ord-94a37b6ce0174e59aa058357022cccea
Source dataset
uspto-grants-2013_10
Patent number
US08569294B2

Reaction notes

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