Acetic Acid → (3S,4S)-4-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-ylmethyl]-tetrahydro-pyran-3-ylamine

[(S)-3-(4-Fluoro-benzyl)-piperidin-1-yl]-[(3S,4R)-3-aminotetrahydro-pyran-4-yl]-methanone (367 mg, 1.14 mmol) was treated with borane-tetrahydrofuran complex in tetrahydrofuran (1.0 M; 46 mL, 46 mmol) and stirred for 20 h . The mixture was treated slowly with 20% acetic acid in methanol (25 mL), and the resulting mixture was stirred at room temperature for 3 h . The solvents were removed, and the residue was dissolved in water, made basic (pH 11) with 50% sodium hydroxide, and extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and concentrated to provide a gum (313 mg). A portion of this material (175 mg) was purified by flash column chromatography (5% methanol/dichloromethane, containing 0.5% ammonium hydroxide) to provide the product (103 mg, 52%) as an oil which solidified on standing. 1H NMR (300 mHz, CD3OD) δ7.15 (m, 2H), 6.98 (m, 2H), 3.87 (dd, J=10.3, 3.6 Hz, 1H), 3.78 (dd, J=11.1, 4.4 Hz, 1H), 3.37 (dd, J=12.0, 2.4 Hz, 1H), 3.03 (bd, 1H), 3.00 (dd, J=11.0, 10.2 Hz, 1H), 2.78 (bd, 1H), 2.59 (m, 1H), 2.49 (d, J=6.6 Hz, 2H), 2.42 (dd, J=12.8, 8.8 Hz, 1H), 2.23 (dd, J=12.8, 4.4 Hz, 1H), 1.9-1.4 (8H), 1.2 (m, 1H), 1.0 (m, 1H), ESI MS: (M+H)+=307.1.

1. stirringthe resulting mixture was stirred at room temperature for 3 h
2. customThe solvents were removed
3. dissolutionthe residue was dissolved in water
4. extractionextracted with dichloromethane
5. dry with materialThe combined organic phases were dried (Na2SO4)
6. concentrationconcentrated

ORD record

ord-806282136f384d00bb46e5b1b9913bde

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06627629B2