Potassium tert-butoxide → 2-tert-butyl-5-chloro-1H-pyrrolo[3,2-b]pyridine

HRID 1043998Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]([CH3:13])([CH3:12])[CH3:11])[C:5]([NH:14]C(=O)CCC)=[CH:4][CH:3]=1.CC([O-])(C)C.[K+]>CN(C=O)C>[C:10]([C:9]1[NH:14][C:5]2[C:6](=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:8]=1)([CH3:13])([CH3:12])[CH3:11]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of crude N-[6-chloro-2-(3,3-dimethyl-but-1-ynyl)-pyridin-3-yl]-butyramide (16 g) in DMF (150 mL) was added t-BuOK (12.4 g, 110 mmol) at room temperature. The mixture was heated at 70° C. for 1 hour. The solvent was removed by evaporation under vacuum. Water (100 mL) and ethyl acetate (200 mL) were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 10:1) to give 2-tert-butyl-5-chloro-1H-pyrrolo[3,2-b]pyridine (10.8 g, two steps: 94%). 1H NMR (CDCl3, 400 MHz) δ 8.52 (brs, 1H), 7.28 (d, J=8.4 Hz, 1H), 7.02 (d, J=8.4 Hz, 1H), 6.37 (d, J=2.0 Hz, 1H), 1.40 (s, 9H).

Workup

customThe solvent was removed by evaporation under vacuum
additionWater (100 mL) and ethyl acetate (200 mL) were added
customThe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate (100 mL×3)
dry with materialThe combined organic layers were dried over anhydrous Na2SO4
customevaporated under vacuum
customto give the crude product, which
customwas purified by column chromatography on silica gel (petroleum ether/ethyl acetate 10:1)

Sources & evidence

ORD record: ord-a3f7fad92acc4576ab00f3d8426c53cb
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08563573B2

Reaction notes

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