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) δ 7.03, 3.63, 3.57, 2.42; 13C NMR (100 MHz, CDCl3) δ 140.9, 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-Eintrag

ord-1f15c4f0eb3a4a8e9d5cd59c6f7b1072

Quelldatensatz

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06559145B2