Trimethyl borate → Dimethyl[5-(benzyloxy)-1-(biphenyl-3-yl)-4-oxo-1,4-dihydropyridin-3-yl]boronate

HRID 1056886Notes

Reaction equation

HRID 1056886 reaction equation
[Cl-].[Li+].[CH2:3]([O:10][C:11]1[C:16](=[O:17])[C:15](Br)=[CH:14][N:13]([C:19]2[CH:20]=[C:21]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:22]=[CH:23][CH:24]=2)[CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:31][O:32][B:33](OC)[O:34][CH3:35]>C1COCC1>[CH3:31][O:32][B:33]([C:15]1[C:16](=[O:17])[C:11]([O:10][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[CH:12][N:13]([C:19]2[CH:20]=[C:21]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:22]=[CH:23][CH:24]=2)[CH:14]=1)[O:34][CH3:35]

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 433294Lithium ChlorideHCID 674201973-(benzyloxy)-1-(biphenyl-3-yl)-5-bromopyridin-4(1H)-one

Product 1

HCID 67404775Dimethyl[5-(benzyloxy)-1-(biphenyl-3-yl)-4-oxo-1,4-dihydropyridin-3-yl]boronate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium chloride (515 mg, 12.1 mmol) in a 25 mL round bottom flask under high vacuum was heated with a heat gun until a free flowing granular solid was obtained (˜5 min). The flask was cooled to room temperature, purged with N2, and treated with isopropylmagnesium chloride (6.1 mL of a 2 M solution in THF). After stirring at room temperature for 1 h, the mixture was cooled to −10° C. and treated with 3-(benzyloxy)-1-(biphenyl-3-yl)-5-bromopyridin-4(1H)-one (1.05 g, 2.4 mmol) as a suspension in 3.5 mL of THF. After stirring for 0.5 h, trimethylborate (1.35 mL, 12.1 mmol) was added drop wise and the reaction mixture was stirred an additional 3.5 h, before being quenched with the addition of MeOH (12 mL) to provide a solution of crude dimethyl[5-(benzyloxy)-1-(biphenyl-3-yl)-4-oxo-1,4-dihydropyridin-3-yl]boronate which was used directly in the subsequent step. LC/S (M+H)+ 398.

Workup

  1. customwas obtained (˜5 min)
  2. custompurged with N2
  3. additiontreated with isopropylmagnesium chloride (6.1 mL of a 2 M solution in THF)
  4. temperaturethe mixture was cooled to −10° C.
  5. stirringAfter stirring for 0.5 h
  6. stirringthe reaction mixture was stirred an additional 3.5 h
  7. custombefore being quenched with the addition of MeOH (12 mL)

Sources & evidence

ORD record
ord-e09f1a62300143f6ab5a8ce1c6fc7b04
Source dataset
uspto-grants-2016_07
Patent number
US09399651B2

Reaction notes

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