8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-carbaldehyde → 1-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-yl]ethanol

HRID 1530730Notes

Reaction equation

[CH3:1][Mg]Br.[F:4][C:5]1[C:27]([CH:28]=[O:29])=[CH:26][C:8]2[C:9]3[N:13]([CH2:14][CH2:15][O:16][C:7]=2[CH:6]=1)[CH:12]=[C:11]([C:17]1[N:18]([CH:23]([CH3:25])[CH3:24])[N:19]=[C:20]([CH3:22])[N:21]=1)[N:10]=3>C1COCC1.C1(C)C=CC=CC=1.C1COCC1>[F:4][C:5]1[C:27]([CH:28]([OH:29])[CH3:1])=[CH:26][C:8]2[C:9]3[N:13]([CH2:14][CH2:15][O:16][C:7]=2[CH:6]=1)[CH:12]=[C:11]([C:17]1[N:18]([CH:23]([CH3:25])[CH3:24])[N:19]=[C:20]([CH3:22])[N:21]=1)[N:10]=3

Participants

Conditions

Temperature: 0 °C

Procedure

Methylmagnesium bromide (10.1 mL of a 1.4 M solution in THF/PhMe) was added to a solution of 8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-carbaldehyde (968 mg, 2.83 mmol) in THF (20 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h and then quenched by addition of sat. NH4Cl (10 mL). The mixture was extracted with EtOAc (3×25 mL) and the combined organics were washed (brine), dried (Na2SO4) and concentrated in vacuo. Compound purified by column chromatography (Si-PPC, gradient 0-5% MeOH in DCM) to give the title compound (361 mg, 0.97 mmol, 34%) as a pale brown solid. LCMS (Method J): RT=2.53 min, [M+H]+=372

Workup

customquenched by addition of sat. NH4Cl (10 mL)
extractionThe mixture was extracted with EtOAc (3×25 mL)
washthe combined organics were washed (brine)
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customCompound purified by column chromatography (Si-PPC, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record: ord-5a0ce72e57b346149da1bfc618d119d5
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090628B2

Reaction notes

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