Triethylamine → 4-[(2R)-2-(4-bromophenyl)-2-chloroethyl]morpholine

To a stirred 0° C. solution of (1R)-1-(4-Bromophenyl)-2-(4-morpholinyl)ethanol (48.5 g, 0.17 mol) in 200 mL CH2Cl2 was added 52 mL of triethylamine (0.37 mol, 2.2 equiv). Following the addition of triethylamine, 15.8 mL of methanesulfonyl chloride (0.2 mol, 1.2 equiv) was added to the reaction mixture through an addition funnel. After the addition, the reaction mixture was stirred at room temperature overnight. HPLC analysis indicated a 5:1 ratio of starting material to product and an additional 6.58 mL of methanesulfonyl chloride (0.085 mols) and 11.8 mL of triethylamine (0.085 mol) were added. After stirring overnight at ambient temperature, the reaction was heated to 40° C. and stirred for 48 h. The reaction mixture was concentrated, and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude brown oil was purified by silica gel chromatography (800 g silica gel 60, 230-400 mesh, 20-50% EtOAc/CH2Cl2 as eluent). Concentration of the pure fractions yielded the title compound as a yellow oil (34.5 g, 67%). MS (ES) m/e 304, 306 [M+H]+.

1. additionwas added to the reaction mixture through an addition funnel
2. additionAfter the addition
3. stirringAfter stirring overnight at ambient temperature
4. temperaturethe reaction was heated to 40° C.
5. stirringstirred for 48 h
6. concentrationThe reaction mixture was concentrated
7. customthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
8. washThe organic layer was washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude brown oil was purified by silica gel chromatography (800 g silica gel 60, 230-400 mesh, 20-50% EtOAc/CH2Cl2 as eluent)

ORDレコード

ord-d09d4899b99a41f1b4d092eefe81b061

出典データセット

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07749998B2