Triphenylphosphine → 1-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine

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(3aS,4S,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (1-1) (250 mg, 1.6 mmol, 1 equiv) was dissolved in dry THF (8 mL). Triphenylphosphine (630 mg, 2.4 mmol, 1.5 equiv) was added, followed by 4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4, 300 mg, 1.9 mmol, 1.2 equiv). The mixture was cooled to 0° C. and DIAD (470 μL, 2.4 mmol, 1.5 equiv) was added dropwise. The resulting mixture was stirred at ambient temperature for 2 hours. The solvent was removed at reduced pressure and the yellow residue was purified via flash chromatography on a 80 g silica gel column (gradient elution 0 to 100% ethyl acetate in hexanes) to yield 1-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine (2-2) and 3-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-3H-imidazo[4,5-c]pyridine (2-1) as a 1:1 regioisomeric mixture. 1H NMR (2-2) (500 MHz, CDCl3): δ 7.82 (s, 1H); 7.86 (m, 1H); 6.42 (d, J=5.7 Hz, 1H); 6.05 (s, 1H); 5.75 (s, 1H); 5.44 (d, J=5.5 Hz, 1H); 4.68 (d, J=5.7 Hz, 1H); 1.51 (s, 3H); 1.37 (s, 3H). LRMS m/z (M+H) 294.0 found, 294.1 required. 1H NMR (2-1) (500 MHz, CDCl3): δ 7.90 (s, 1H); 7.84 (m, 1H); 6.42 (d, J=5.7 Hz, 1H); 6.05 (s, 1H); 5.75 (s, 1H); 5.44 (d, J=5.5 Hz, 1H); 4.68 (d, J=5.7 Hz, 1H); 1.51 (s, 3H); 1.37 (s, 3H). LRMS m/z (M+H) 294.0 found, 294.1 required.

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