3-Fluoro-5-methylpyridine

General procedure: An oven-dried reaction vessel (4 or 9 ml screw-cap vial) equipped with a stirring bar was allowed to cool to room temperature under vacuum. Activated 4 A molecular sieves (crushed, 50 mg), [Rh-2 ] (and solid substrates, 1.0 equiv.), were added under air. The vial was then depressurized and pressurized with argon gas three times before the addition of dry THF (1 M) (and liquid substrates, distilled over CaH2, 1.0 equiv.). Following the addition of 4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (2.0-4.0 equiv. as indicated), the glass vial was placed in a 150 ml stainless-steel autoclave under an argon atmosphere. The autoclave was pressurized and depressurized with hydrogen gas three times before the indicated pressure was set. The reaction mixture was stirred at 25-40 C for 24 h. After the autoclave was carefully depressurized, trifluoroacetic anhydride (3.0 equiv.) and CH2Cl2 (0.5 ml) were added to the crude mixture and stirring was continued for 10 min at room temperature. Alternatively, di-tert-butyl dicarbonate (3.0 equiv.), triethyl amine (3.0 equiv.) and CH2Cl2 (0.5 ml) were added to the reaction mixture and stirring was continued for 2 h at room temperature. The crude was then filtered over fritted funnel and the remaining solid was washed with ethyl acetate (2x 5 ml). The combined solution was concentrated under reduced pressure and submitted to column chromatography (pentane/ethyl acetate or pentane/dichloromethane) to obtain the final product. The indicated diastereoselectivities were determined by GC analysis or from the 19F NMR spectrum immediately after the reaction. NMR yield was calculated using hexafluorobenzene (20 mul, 0.173 mmol) as internal standard.General procedure: An oven-dried reaction vessel (4 or 9 ml screw-cap vial) equipped with a stirring bar was allowed to cool to room temperature under vacuum. Activated 4 A molecular sieves (crushed, 50 mg), [Rh-2 ] (and solid substrates, 1.0 equiv.), were added under air. The vial was then depressurized and pressurized with argon gas three times before the addition of dry THF (1 M) (and liquid substrates, distilled over CaH2, 1.0 equiv.). Following the addition of 4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (2.0-4.0 equiv. as indicated), the glass vial was placed in a 150 ml stainless-steel autoclave under an argon atmosphere. The autoclave was pressurized and depressurized with hydrogen gas three times before the indicated pressure was set. The reaction mixture was stirred at 25-40 C for 24 h. After the autoclave was carefully depressurized, trifluoroacetic anhydride (3.0 equiv.) and CH2Cl2 (0.5 ml) were added to the crude mixture and stirring was continued for 10 min at room temperature. Alternatively, di-tert-butyl dicarbonate (3.0 equiv.), triethyl amine (3.0 equiv.) and CH2Cl2 (0.5 ml) were added to the reaction mixture and stirring was continued for 2 h at room temperature. The crude was then filtered over fritted funnel and the remaining solid was washed with ethyl acetate (2x 5 ml). The combined solution was concentrated under reduced pressure and submitted to column chromatography (pentane/ethyl acetate or pentane/dichloromethane) to obtain the final product. The indicated diastereoselectivities were determined by GC analysis or from the 19F NMR spectrum immediately after the reaction. NMR yield was calculated using hexafluorobenzene (20 mul, 0.173 mmol) as internal standard.Preparation of tert-butyl 4-((5-fluoropyridin-3-yl )methvn-4- hydroxypiperidine-l-carboxylate. A solution of (1.6 g) was treated with freshly prepared LDA and methyl formate at -78C for five hours to yield 3-fluoro-5-methylisonicotinaldehyde (700 mg).

Molecular Weight:111.12
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Exact Mass:111.048427358
Monoisotopic Mass:111.048427358
Topological Polar Surface Area:12.9
Heavy Atom Count:8
Complexity:74.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes