Methylamine → (3-Chloro-4-fluoro-benzo[b]thiophen-2-ylmethyl)methylamine

A solution of 3-chloro-4-fluoro-benzo[b]thiophene-2-carbaldehyde (880 mg, 4.04 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 (30 mL), and after cooling in an ice bath, NaBH4 (153 mg, 4.04 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 (30 mL) and the mixture was 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 (443 mg, 48%) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.54 (dd, J=8.0, 0.6 Hz, 1H), 7.27 (ddd, J=8.0, 8.0, 4.6 Hz, 1H), 7.03 (ddd, J=11.4, 8.0, 0.6 Hz, 1H), 4.05 (s, 2H), 2.53 (s, 3H), 1.55 (s, 1H).

1. concentrationThe mixture was concentrated
2. dissolutionThe residue was dissolved in EtOH (30 mL)
3. temperatureafter cooling in an ice bath
4. concentrationThe mixture was concentrated
5. extractionthe mixture was 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-b4df8d0801294021989f02dcc6364eb8

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07879872B2