Trimethyl borate → [2-Methoxy-5-[4-(methoxycarbonyl)-2-methylphenyl]phenyl]boronic acid

HRID 1508560Notes

Reaction equation

I[C:2]1[CH:3]=[C:4]([C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]=2[CH3:20])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].C([Mg]Cl)(C)C.[B:26](OC)([O:29]C)[O:27]C>O1CCCC1>[CH3:9][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]=2[CH3:20])=[CH:3][C:2]=1[B:26]([OH:29])[OH:27]

Participants

Conditions

Temperature: -15 °C

Procedure

Into a 10000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of methyl 4-(3-iodo-4-methoxyphenyl)-3-methylbenzoate (600 g, 1.57 mol, 1.00 equiv) in tetrahydrofuran (5000 mL). This was followed by the addition of isopropyl magnesium chloride (960 mL, 1.20 equiv) dropwise with stirring at <−25° C. over 60 min. The reaction was maintained for 1 h at −15° C., followed by addition of trimethyl borate (329.2 g, 3.17 mol, 2.00 equiv) dropwise with stirring at <−20° C. over 30 min. The resulting solution was stirred for 60 min at <0° C., then quenched by the addition of 5000 mL of H3PO4 (aq. 1M). The bulk of THF was removed under vacuum. The solid was collected by filtration and washed with 2×200 ml of toluene. This resulted in 300 g (crude) of [2-methoxy-5-[4-(methoxycarbonyl)-2-methylphenyl]phenyl]boronic acid as a yellow solid.

Workup

customInto a 10000-mL 4-necked round-bottom flask purged
temperaturemaintained with an inert atmosphere of nitrogen
stirringwith stirring at <−20° C. over 30 min
stirringThe resulting solution was stirred for 60 min at <0° C.
customquenched by the addition of 5000 mL of H3PO4 (aq. 1M)
customThe bulk of THF was removed under vacuum
filtrationThe solid was collected by filtration
washwashed with 2×200 ml of toluene
customThis resulted in 300 g (crude) of [2-methoxy-5-[4-(methoxycarbonyl)-2-methylphenyl]phenyl]boronic acid as a yellow solid

Sources & evidence

ORD record: ord-4e68bc8868fd482d8c72bc4af654769d
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221834B2

Reaction notes

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