Trimethyl borate → [5-(Benzyloxy)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl]boronic acid

HRID 625952Notes

Reaction equation

C([Mg]Cl)(C)C.[Li+].[Cl-].[CH2:8]([O:15][C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20](Br)[CH:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C[O:26][B:27](OC)[O:28]C>C1COCC1>[CH2:8]([O:15][C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([B:27]([OH:28])[OH:26])[CH:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of isopropylmagnesium chloride (2 M in THF, 2.04 mL) was added LiCl (173 mg, 4.08 mmol) and the resulting solution was stirred for 1 h. THF (3 mL) was added to this solution, cooled to −10° C. Solid 3-(benzyloxy)-5-bromo-1-methylpyridin-2(1H)-one (400 mg, 1.36 mmol) was added and stirred for 1 h. Trimethylborate (0.456 mL, 4.08 mmol) was added to the reaction mixture, stirred at −10° C. for 1 h and then quenched with cone HCl (0.6 mL). The cooling bath was removed, stirred at room temperature overnight and concentrated. Purification by preparative HPLC (5-95% CH3CN/H2O over 20 min, 0.05% added TFA) afforded 276 mg [5-(benzyloxy)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl]boronic acid (78%) as a white solid. LC/MS (M+H)+260.2.

Workup

stirringstirred for 1 h
stirringstirred at −10° C. for 1 h
customquenched with cone HCl (0.6 mL)
customThe cooling bath was removed
stirringstirred at room temperature overnight
concentrationconcentrated
customPurification
additionby preparative HPLC (5-95% CH3CN/H2O over 20 min, 0.05% added TFA)

Sources & evidence

ORD record: ord-20b56022105545108ce0bb2d7ec48954
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309199B2

Reaction notes

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