Acetic Acid → 4-((4-Bromo-5-chlorothiophen-2-yl)methyl)morpholine

Morpholine (15.2 mL), acetic acid (9.1 mL), and then sodium triacetoxyborohydride (50.3 g) is added to a solution of 4-bromo-5-chloro-2-thiophenecarbaldehyde (Preparation 61, 35.7 g) in 1,2-dichloroethane (600 mL) at 0° C. The mixture is allowed to warm to room temperature, and after 18 h, it is quenched with a 2N NaOH solution (200 mL) with ice bath cooling. The organic layer is separated and washed with 1 N NaOH solution (2×200 mL). The aqueous layers are extracted with CH2Cl2 (2×100 mL). The combined organic layers are extracted with 0.25 M HCl solution (2 L) and the resulting aqueous layer is made basic with 2N NaOH solution. The mixture is then extracted with CH2Cl2 (2 L) and the organic layer is dried (Na2SO4) and concentrated to afford 39.24 g (84%) of the title compound as a light yellow oil. Physical characteristics: 1H NMR (400 MHz, DMSO-d6) δ7.03, 3.63, 3.57, 2.42; 13C NMR (100 MHz, CDCl3) δ140.9, 127.3, 125.9, 109.2, 66.9, 57.6, 53.3; MS (ESI+) m/z 296 (72, (M+H)+), 298 (100).

1. customit is quenched with a 2N NaOH solution (200 mL) with ice bath
2. temperaturecooling
3. customThe organic layer is separated
4. washwashed with 1 N NaOH solution (2×200 mL)
5. extractionThe aqueous layers are extracted with CH2Cl2 (2×100 mL)
6. extractionThe combined organic layers are extracted with 0.25 M HCl solution (2 L)
7. extractionThe mixture is then extracted with CH2Cl2 (2 L)
8. dry with materialthe organic layer is dried (Na2SO4)
9. concentrationconcentrated

ORD record

ord-8d23e1d86f1240a2932100cae3434269

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06903097B2