3,4-dihydro-2H-pyran → (2R)-1-morpholino-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-one

HRID 379656

Reaction equation

HRID 379656 reaction equation
[O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.[OH:7][C@H:8]([CH3:17])[C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:10].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[O:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[O:7][C@H:8]([CH3:17])[C:9]([N:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1)=[O:10]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 14978393(R)-2-Hydroxy-1-morpholinopropan-1-one

Product 1

HCID 10977653(2R)-1-morpholino-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-oneYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3,4-Dihydro-2H-pyran (90.5 ml, 1.2 eq) was added dropwise to a mixture of 4-[(R)-2-hydroxypropionyl]morpholine (132 g) and p-toluenesulfonic acid monohydrate (500 mg, 0.003 eq) in dry dichloromethane (500 ml) over a period of 15 min with stirring at 0° C. After being stirred for 30 min at 0° C., the mixture was washed with aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification of the residue by silica gel chromatography, using n-hexane: ethyl acetate (8:1)˜ethyl acetate as an eluent, gave 4-[(2R)-2-(3,4,5,6-Tetrahydro-2H-pyran-2-yloxy)propionyl]morpholine (191.6 g, 95% yield) as a pale yellow oil.

Workup

  1. stirringAfter being stirred for 30 min at 0° C.
  2. washthe mixture was washed with aqueous sodium bicarbonate
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the residue by silica gel chromatography

Sources & evidence

ORD record
ord-99c1990a46ee403da016a260d508eb23
Source dataset
uspto-grants-2001_10
Patent number
US06300353B1

Linked notes

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