Diisobutylaluminumhydride → 7-bromo-3-chloro-1-fluoro-5-(2-hydroxyethyl)-5H-chromeno[2,3-c]pyridin-5-ol

HRID 931577Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=[CH:16][CH:17]=1)[O:14][C:7]1[C:8]([F:13])=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]2([CH2:19][C:20](OC(C)(C)C)=[O:21])[OH:18].[H-].C([Al+]CC(C)C)C(C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=[CH:16][CH:17]=1)[O:14][C:7]1[C:8]([F:13])=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]2([CH2:19][CH2:20][OH:21])[OH:18]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of tert-butyl 2-(7-bromo-3-chloro-1-fluoro-5-hydroxy-5H-chromeno[2,3-c]pyridin-5-yl)acetate (66 g, 148 mmol) in THF (200 mL) was cooled to −78° C. followed by the drop wise addition of diisobutylaluminum hydride (1.0 M solution in THF; 180 ml, 180 mmol). The resulting reaction mixture was cooled to 0° C. and stirred for 2 h. The reaction mixture was quenched with aqueous, saturated NH4Cl solution and extracted with EtOAc. The combined organics were dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by chromatography (0-50% EtOAc/hexanes) to afford 7-bromo-3-chloro-1-fluoro-5-(2-hydroxyethyl)-5H-chromeno[2,3-c]pyridin-5-ol (48 g, 128 mmol, 86% yield) as a light yellow solid.

Workup

customThe resulting reaction mixture
customThe reaction mixture was quenched with aqueous, saturated NH4Cl solution
extractionextracted with EtOAc
dry with materialThe combined organics were dried over Na2SO4
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by chromatography (0-50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-d04fcfb892944473afcd5a87816db6b0
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296759B2

Reaction notes

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