Hydrochloric Acid → (2RS,5R)-4-(4-methoxybenzyl)-5-methyl-2-phenylmorpholin-3-one

HRID 1045699Notes

Reaction equation

Cl[CH:2]([CH3:6])[C:3](Cl)=[O:4].[CH3:7][O:8][C:9]1[CH:20]=[CH:19][C:12]([CH2:13][NH:14][C@H:15]([CH3:18])[CH2:16][OH:17])=[CH:11][CH:10]=1.C(N([CH2:26][CH3:27])CC)C.C[O-].[Na+].CO.Cl.O1C[CH2:37][CH2:36][CH2:35]1>O>[CH3:7][O:8][C:9]1[CH:20]=[CH:19][C:12]([CH2:13][N:14]2[C@H:15]([CH3:18])[CH2:16][O:17][CH:2]([C:6]3[CH:27]=[CH:26][CH:37]=[CH:36][CH:35]=3)[C:3]2=[O:4])=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

2-Chloro-2-methylacetyl chloride (8.4 g, 40.0 mmol) was added to a solution of (2R)-2-(4-methoxybenzylamino)-propan-1-ol (7.79 g, 39.9 mmol) and triethylamine (4.5 g, 44.5 mmol) in tetrahydrofuran (100 ml) and the solution was stirred for one hour. The solution was cooled at 0° C. and 28% sodium methoxide in methanol solution (15.4 g, 79.8 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; 30-50% ethyl acetate in hexane) to afford (2RS,5R)-4-(4-methoxybenzyl)-5-methyl-2-phenylmorpholin-3-one (12.2 g, 39.1 mmol, 98%) 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; 30-50% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-8f9395950cc948c39e4aca2a637c8a7e
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569294B2

Reaction notes

Loading…