Methylamine → (3-Chloro-7-fluoro-benzo[b]thiophen-2-ylmethyl)methylamine

A solution of 3-chloro-7-fluoro-benzo[b]thiophene-2-carbaldehyde (610 mg, 2.78 mmol) in CH3NH2 (20 mL of a 2.0 M solution in MeOH, 40 mmol) was stirred at room temperature overnight. The mixture was concentrated. The residue was dissolved in EtOH (20 mL), and after cooling in an ice bath, NaBH4 (159 mg, 4.20 mmol) was added. The mixture was slowly warmed to room temperature and then stirred overnight. The mixture was concentrated. The residue was taken up in NaOH (20 mL) and the mixture extracted with Et2O (3×). The combined organics were washed with satd NaCl, dried (Na2SO4) and concentrated. Purification by column chromatography (silica gel, 95:5 CH2Cl2/MeOH) gave the title compound (460 g, 70%) as a brown oil: 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J=8.0 Hz, 1H), 7.38 (ddd, J=7.9, 7.9, 4.9 Hz, 1H), 7.06 (dd, J=8.8, 8.8 Hz, 1H), 4.09 (s, 2H), 2.53 (s, 3H), 1.55 (s, 1H).

1. concentrationThe mixture was concentrated
2. dissolutionThe residue was dissolved in EtOH (20 mL)
3. temperatureafter cooling in an ice bath
4. concentrationThe mixture was concentrated
5. extractionthe mixture extracted with Et2O (3×)
6. washThe combined organics were washed with satd NaCl
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. customPurification by column chromatography (silica gel, 95:5 CH2Cl2/MeOH)

ORD record

ord-f8c76bc571e440e88c3f622b31aa401a

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450307B2