Sodium hydride → 8-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine

HRID 2369495Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of NaH (389 mg, 9.72 mmol) in THF (9 mL) cooled to 0° C., was added (4-(4-chloro-2-fluorophenyl)pyridin-3-yl)(cyclopropyl)methanol (900 mg, 3.24 mmol) in THF (9 mL) dropwise over a period of 10 min. The reaction mixture was stirred at 0° C. for 15 min and then warmed to room temperature and stirred for 15 h. The reaction mixture was quenched by addition of cold water (10 mL) and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with brine (1×25 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified via silica gel column chromatography (ethyl acetate/hexanes) to give 8-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine (630 mg, 2.45 mmol, 75% yield). LCMS (ESI) m/e 258.0 [(M+H)+, calcd for C15H13ClNO 258.1]; LC/MS retention time (Method C): tR=2.08 min.

Workup

temperaturewarmed to room temperature
stirringstirred for 15 h
customThe reaction mixture was quenched by addition of cold water (10 mL)
extractionextracted with ethyl acetate (3×25 mL)
washThe combined organic extracts were washed with brine (1×25 mL)
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
customThe crude residue was purified via silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-7e1a035927334e4387de5f541334e4dd
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08703953B2

Reaction notes

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