Hydrochloric Acid → (5R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one

HRID 1045667Notes

Reaction equation

Cl[CH2:2][C:3](Cl)=[O:4].[CH3:6][O:7][C:8]1[CH:19]=[CH:18][C:11]([CH2:12][NH:13][C@H:14]([CH3:17])[CH2:15][OH:16])=[CH:10][CH:9]=1.C(N(CC)CC)C.[H-].[Na+].Cl>O1CCCC1.O>[CH3:6][O:7][C:8]1[CH:19]=[CH:18][C:11]([CH2:12][N:13]2[C@H:14]([CH3:17])[CH2:15][O:16][CH2:2][C:3]2=[O:4])=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Chloroacetyl chloride (15 g, 133 mmol) was added to a solution of (2R)-2-(4-methoxybenzylamino)-propan-1-ol (26 g, 133 mmol) and triethylamine (15 g, 148 mmol) in tetrahydrofuran (200 ml) and the solution was stirred for one hour. The solution was cooled at 0° C. and sodium hydride (60% dispersion in mineral oil, 5.8 g, 145 mol) was added. When the reaction was complete (checked by thin layer chromatography), excess reagent was decomposed by the addition of water and pH was adjusted to 5-6 with 3N aqueous hydrochloric acid. The solution was partitioned between water and chloroform. 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-methylmorpholin-3-one (19.6 g, 83.3 mmol, 63%) as colorless oil.

Workup

customThe solution was partitioned between water and chloroform
washThe organic layer was washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform)

Sources & evidence

ORD record: ord-5cc975fa08ff492baaf511a98192b5f3
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569294B2

Reaction notes

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