Benzaldehyde → 1h-Pyrrolo[2,3-c]pyridine-2-methanol,a-phenyl-1-(phenylsulfonyl)-

Temperature

10 °C

To a solution of lithium diisopropylamide (1.2 mL of a 2 M solution in THF/heptane, 2.3 mmol) in THF (3 mL) was added a solution of 1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (300 mg, 1.2 mmol) and N,N,N′,N′-tetramethylethylenediamine (0.18 mL, 1.2 mmol) in THF (5 mL), dropwise at −25° C. After 0.5 h, a solution of benzaldehyde (0.24 mL, 2.3 mmol) in THF (6 mL) was added dropwise. After 1 h, the reaction mixture was warmed to 10° C. and quenched by the addition of saturated NH4Cl (5 mL). The reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (2×40 mL). The combined extracts were dried (Na2SO4) and concentrated under reduced pressure. Purification by column chromatography (silica gel, 9:1 hexanes/EtOAc to EtOAc) gave phenyl[1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridin-2-yl]methanol (155 mg, 37%) as a mixture of enantiomers: 1H NMR (500 MHz, DMSO-d6) δ 6.36 (1H, d, J=5.5 Hz), 6.43 (1H, d, J=5.5 Hz), 6.75 (1H, s), 7.32-7.36 (5H, m), 7.53 (2H, dd, J=8.4, 7.6 Hz), 7.59 (1H, d, J=5.2 Hz), 7.66-7.70 (1H, m), 7.82-7.85 (2H, m), 8.35 (1H, d, J=5.2 Hz), 9.22 (1H, s); ESI MS m/z 365 [C20H16N2O3S+H]+; HPLC (Method A) 91.9% (AUC), tR=16.5 min.

1. customdropwise at −25° C
2. waitAfter 1 h
3. customquenched by the addition of saturated NH4Cl (5 mL)
4. additionThe reaction mixture was diluted with H2O (20 mL)
5. extractionextracted with EtOAc (2×40 mL)
6. dry with materialThe combined extracts were dried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. customPurification by column chromatography (silica gel, 9:1 hexanes/EtOAc to EtOAc)

ORD record

ord-8f631f3f17e14534b71250e5da3ee223

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07608627B2