Epichlorohydrin → HCID 58650607, compound

A mixture of (2S)-2-[benzylamino]propan-1-ol (1 equivalent) and epichlorohydrin (1 equivalent) was stirred at room temperature overnight. The mixture was cooled down to 0° C. and cold trifluoromethanesulfonic acid (4 equivalents) was added. The flask was equipped with a reflux condenser and the mixture was stirred at 160° C. overnight. The reaction mixture was cooled to room temperature, diluted with CH2Cl2 and quenched with ice water. The mixture was then made basic (pH=12) with a 30% NaOH solution. The two phases were separated, and the aqueous phase was extracted with CH2Cl2. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated to afford a dark brown oil. The crude product contained an equimolar mixture of (2R,5S)-2-(chloromethyl)-5-methyl-4-benzylmorpholine(cis diastereoisomer) and (2S,5S)-2-(chloromethyl)-5-methyl-4-benzylmorpholine(trans diastereoisomer), which were separated by chromatography on silica gel (ethyl acetate/hexanes 1:20 to 1:8). (2S,5S)-2-(chloromethyl)-5-methyl-4-benzyl morpholine was obtained as the isomer with the lower Rf. GC/MS: 239 (15%, M+), Rt=15.08 minutes; LC/MS (m/z): 240.0 (MH+), Rt 1.56 minutes.

1. temperatureThe mixture was cooled down to 0° C.
2. customThe flask was equipped with a reflux condenser
3. stirringthe mixture was stirred at 160° C. overnight
4. temperatureThe reaction mixture was cooled to room temperature
5. customquenched with ice water
6. customThe two phases were separated
7. extractionthe aqueous phase was extracted with CH2Cl2
8. washThe organic layer was washed with water, brine
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. customto afford a dark brown oil
12. customwere separated by chromatography on silica gel (ethyl acetate/hexanes 1:20 to 1:8)

ORD record

ord-eef9b7806f67477aae34159bfb28693d

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07642278B2