Sodium hydride → 4-Chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1627986Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.[H-].[Na+].[CH3:13][CH:14]([Si:16](Cl)([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[CH3:15]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([Si:16]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:15])[CH3:13])[CH:9]=[CH:10][C:3]=12

Participants

Conditions

Temperature: 0 °C

Procedure

A flask was charged with 4-chloro-1H-pyrrolo[2,3-b]pyridine (6.0 g, 39 mmol, Arkpharm) and THF (100 mL). The mixture was cooled to about 0° C. and 60 wt % NaH (1.89 g, 47.2 mmol) was added portion-wise. The mixture was warmed to rt and after about 45 min. TIPSCl (12.5 mL, 59.0 mmol) was added drop-wise and mixture was allowed to stir overnight at rt. The mixture was quenched with water (100 mL) and extracted with EtOAc (200 mL). The organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography with a gradient of 0 to 10% EtOAc/heptane to give 4-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (11.0 g, 91%): 1H NMR (d-DMSO) δ 8.20 (d, J=5.17 Hz, 1H), 7.59 (d, J=3.55 Hz, 1H), 7.23 (d, J=5.16 Hz, 1H), 6.68 (d, J=3.50 Hz, 1H), 1.83 (m, 3H), 1.06 (m, 18H).

Workup

temperatureThe mixture was warmed to rt and after about 45 min
customThe mixture was quenched with water (100 mL)
extractionextracted with EtOAc (200 mL)
dry with materialThe organic layer was dried over anhydrous MgSO4
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography with a gradient of 0 to 10% EtOAc/heptane

Sources & evidence

ORD record: ord-2273a3fce9d04d9fa0b293af72aafc7c
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785639B2

Reaction notes

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