Identification | Back Directory | [Name]
(5S)-5-Phenyl-2-morpholinone hydrochloride | [CAS]
491833-36-4 | [Synonyms]
Eliglustat intermediate 1 (5S)-5-phenylmorpholin-2-one HCl salt 5-phenylmorpholine-2-one hydrochloride (S)-5-phenylmorpholin-2-one hydrochloride (5S)-5-Phenyl-2-morpholinone hydrochloride (5S)-5-phenylmorpholin-2-one hydrochloride (5S)-5-phenyl morpholine -2-one hydrochloride | [Molecular Formula]
C10H12ClNO2 | [MDL Number]
MFCD27920765 | [MOL File]
491833-36-4.mol | [Molecular Weight]
213.66 |
Hazard Information | Back Directory | [Uses]
(5S)-5-Phenylmorpholin-2-one Hydrochloride is a building block used in various synthetic preparations. It was used as a reactant in the preparation of enantiopure D-amino acids using Mannich-type reaction of phenylmorpholinone as a chiral amine template. | [Synthesis]
General procedure for the synthesis of (S)-5-phenyl-2-morpholinone hydrochloride from phenyl bromoacetate and L-phenylglycinol: Phenyl bromoacetate (862.17 g, 4.0 mol, 1.1 equiv) was dissolved in acetonitrile (1500 mL, reagent grade) and cooled in an ice bath until the internal temperature was below 5 °C. A cold slurry of acetonitrile (2900 mL) with S-(+)-2-phenylglycinol (500 g, 3.65 mol, 1 equiv) and diisopropylethylamine (DIPEA, 1587 mL, 9.11 mol, 2.5 equiv) was added to the above solution in batches. The mixture was stirred at this temperature for 30 min, then the ice bath was removed and stirring was continued for 4 h at room temperature. Subsequently, the solvent was removed under vacuum while maintaining the bath temperature at 25°C. The residue was co-evaporated with ethyl acetate (2 x 500 mL) to give a light yellow viscous oily substance. Ethyl acetate (4500 mL) was added to this oily substance and cooled in an ice bath to an internal temperature below 8 °C. The precipitated solid was filtered and washed with ethyl acetate (3 x 250 mL). The filtrate was cooled to an internal temperature below 5 °C, and dry HCl gas was slowly passed through, keeping the internal temperature below 15 °C, until the pH was below 2 (wet pH paper test). The mixture was continued to be stirred under these conditions for 20 min, followed by filtration to collect the solids. The solid was washed with ethyl acetate (3 x 200 mL) and dried under high vacuum for about 20 h to give the target product (S)-5-phenyl-2-morpholinone hydrochloride 412 g (53% yield). The product was analyzed by 1H NMR and the results were consistent with the structure of (5S)-5-phenylmorpholin-2-one HCl salt. | [References]
[1] Patent: US9546161, 2017, B2. Location in patent: Page/Page column 21 [2] Patent: WO2015/59679, 2015, A1. Location in patent: Page/Page column 13; 14 |
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