3-(2-Fluoropropan-2-yl)-5-((triisopropylsilyloxy)methyl)pyridine → (5-(2-Fluoropropan-2-yl)pyridin-3-yl)methanol
Reaction equation
[F:1][C:2]([C:5]1[CH:6]=[N:7][CH:8]=[C:9]([CH2:11][O:12][Si](C(C)C)(C(C)C)C(C)C)[CH:10]=1)([CH3:4])[CH3:3]>C1COCC1>[F:1][C:2]([C:5]1[CH:10]=[C:9]([CH2:11][OH:12])[CH:8]=[N:7][CH:6]=1)([CH3:4])[CH3:3]Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 1
Procedure
To 2-(5-((triisopropylsilyloxy)methyl)pyridin-3-yl)propan-2-ol (1.1 g, 3.4 mmol) in DCM (30 mL) at −78° C. was added diethylaminosulfur trifluoride (DAST) (0.67 mL, 5.1 mmol) and stirred at the same temperature for 1 hr, then warmed to 0° C. for 3 hrs. The resulting mixture was quenched with MeOH and saturated aqueous NaHCO3. The mixture was extracted with EtOAc three times and dried with anhydrous NaSO4, filtered and concentrated to dryness. Careful purification by flash chromatography (silica gel, hexanes/EtOAc) gave the desired fluoride (3-(2-fluoropropan-2-yl)-5-((triisopropylsilyloxy)methyl)pyridine) as a light yellow solid (0.43 g). 1H NMR (CDCl3): d: 1.127 (d, J=6.3 Hz, 18H), 1.204 (m, 3H), 1.712 (s, 3H), 1.786 (s, 3H), 4.922 (s, 2H), 7.781 (s, 1H), 8.566 (s, 2H). 3-(2-fluoropropan-2-yl)-5-((triisopropylsilyloxy)methyl)pyridine was deprotected with excess aqueous HF in THF to provide (5-(2-fluoropropan-2-yl)pyridin-3-yl)methanol as a white solid. (5-(2-fluoropropan-2-yl)pyridin-3-yl)methanol was then oxidized to 5-(2-fluoropropan-2-yl)nicotinaldehyde using standard Swern Oxidation conditions.
Sources & evidence
- ORD record
- ord-77df42cd784345928c7566c34e612999
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08299267B2
Reaction notes
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