Morpholine → 4-(2-Chloropyridin-3-yl)morpholine

온도

120 °C

A 2-dram vial equipped with a stirbar was charged with Pd(OAc)2 (0.234 g, 1.044 mmol) and rac-BINAP (0.683 g, 1.096 mmol) as solids. Toluene (4 mL) was added via syringe, and the mixture was stirred for 10 min while being degassed with argon, and until a uniform tan suspension resulted. A 100-mL round-bottom flask was charged with 2-chloro-3-iodopyridine (1.25 g, 5.22 mmol) and Cs2CO3 (7.14 g, 21.93 mmol). Toluene (34.8 mL) was added followed by morpholine (0.542 ml, 6.26 mmol). This solution was degassed for 1 min under argon, and then the catalyst/ligand suspension was added via pasteur pipette. A reflux condenser was attached to the flask, and the reaction mixture was refluxed at 120° C. for 16 h. The reaction mixture was concentrated in vacuo, and then diluted with CH2Cl2 (150 mL). The organics were washed with 2×100 mL brine, dried over Na2SO4, filtered, and concentrated in vacuo. The material was purified by gradient elution on silica gel (5 to 75% [5% MeOH/EtOAc] in hexanes) to afford the title compound as light yellow solid (700 mg, 64%). Data for 2-1: 1H NMR (500 MHz, CDCl3) d 8.08 (dd, J=4.4, 1.5 Hz, 1H), 7.32 (dd, J=7.8, 1.5 Hz, 1H), 7.21 (dd, J=7.8, 4.5 Hz, 1H), 3.89 (dd, J=4.5, 4.5 Hz, 4H), 3.08 (dd, J=4.5, 4.5 Hz, 4H); HRMS m/z (M+H) 199.0630 found, 199.0633 required.

1. customA 2-dram vial equipped with a stirbar
2. customwhile being degassed with argon
3. customuntil a uniform tan suspension resulted
4. customThis solution was degassed for 1 min under argon
5. additionthe catalyst/ligand suspension was added via pasteur pipette
6. customA reflux condenser was attached to the flask
7. concentrationThe reaction mixture was concentrated in vacuo
8. additiondiluted with CH2Cl2 (150 mL)
9. washThe organics were washed with 2×100 mL brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe material was purified by gradient elution on silica gel (5 to 75% [5% MeOH/EtOAc] in hexanes)

ORD 기록

ord-0cdaf6bbc2094e84b597aef1566aae32

출처 데이터셋

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08349830B2