Hydrochloric Acid → 6-(Hydroxymethyl)-3-methylbenzofuran-2-carbonitrile

HRID 1773231Notes

Reaction equation

[C:1]([C:3]1[O:4][C:5]2[CH:12]=[C:11]([C:13]([O-])=[O:14])[CH:10]=[CH:9][C:6]=2[C:7]=1[CH3:8])#[N:2].[Cl-].[Cl-].[Ca+2].[BH4-].[Na+].Cl>CCO.C1COCC1>[OH:14][CH2:13][C:11]1[CH:10]=[CH:9][C:6]2[C:7]([CH3:8])=[C:3]([C:1]#[N:2])[O:4][C:5]=2[CH:12]=1

Participants

Conditions

Temperature: 0 °C

Procedure

2-Cyano-3-methylbenzofuran-6-carboxylate (540 mg, 2.51 mmol) was dissolved in 17 mL of EtOH, and CaCl2 (557 mg, 5.02 mmol) was added and the mixture was briefly stirred in the ultrasound bath. Then the mixture was cooled to 0° C. and a solution of NaBH4 (380 mg, 10.04 mmol) in 17 mL of THF was added. The mixture was stirred at 0° C. for 1.5 hr, and then 1N HCl was carefully added. The organic layer was separated, and the aqueous phase was extracted with DCM (4×7 mL), the combined organic phases were dried over Na2SO4, filtered off and evaporated under reduced pressure. The crude product was purified by silica gel flash chromatography 100% DCM-7% MeOH/93% DCM to give 6-(hydroxymethyl)-3-methylbenzofuran-2-carbonitrile (233 mg). 1H NMR (400 MHz, DMSO-d6) δ 2.44 (s, 3H), 4.65 (d, J=5.8 Hz, 2H), 5.42 (t, J=5.8 Hz, 1H), 7.35-7.42 (m, 1H), 7.60 (s, 1H), 7.77 (d, J=8.2 Hz, 1H).

Workup

stirringThe mixture was stirred at 0° C. for 1.5 hr
customThe organic layer was separated
extractionthe aqueous phase was extracted with DCM (4×7 mL)
dry with materialthe combined organic phases were dried over Na2SO4
filtrationfiltered off
customevaporated under reduced pressure
customThe crude product was purified by silica gel flash chromatography 100% DCM-7% MeOH/93% DCM

Sources & evidence

ORD record: ord-98a035785b184c319cb5d563c0b86c0e
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09255093B2

Reaction notes

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