Sodium Bicarbonate → HCID 59497110, compound

HRID 516628Notes

Reaction equation

HRID 516628 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[F:12].CC1(C)C(C)(C)OB([C:21]2[CH2:22][CH2:23][NH:24][CH2:25][CH:26]=2)O1.[C:28]([O-:31])(O)=[O:29].[Na+]>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:5]([O:31][C:28]([N:24]1[CH2:25][CH:26]=[C:21]([C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=2[F:12])[CH2:22][CH2:23]1)=[O:29])([CH3:10])([CH3:6])[CH3:4]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 211054611,2,3,6-Tetrahydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 21951878Methyl 4-bromo-3-fluorobenzoate

Product 1

HCID 59497110HCID 59497110, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 4-bromo-3-fluorobenzoate (2.261 g, 9.702 mmol) [CAS 849758-12-9] was added to a solution of 1,2,3,6-tetrahydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridine (3 g, 9.702 mmol) [CAS 375853-82-0] (synthesis described in WO 2004072025 A2 20040826) in 1,4-dioxane (21 ml) and an aqueous saturated solution of NaHCO3 (18 ml). The resulting solution was degassed using a stream of nitrogen and Pd(PPh3)4 (0.561 g, 0.485 mmol) was added to this solution. The reaction was then microwaved in a sealed tube at 150° C. for 5 minutes. The resulting cooled reaction mixture was then diluted with EtOAc and filtered through a pad of diatomaceous earth. The filtrate was collected, dried over Na2SO4 and concentrated in vacuo. The crude reaction mixture was then purified by column chromatography (silica gel; DCM to DCM/EtOAc up to 6% as eluent). The desired fractions were collected and evaporated in vacuo to yield D22 (2.107 g, 65%).

Workup

  1. customThe resulting solution was degassed
  2. additionwas added to this solution
  3. customThe reaction was then microwaved in a sealed tube at 150° C. for 5 minutes
  4. temperatureThe resulting cooled
  5. customreaction mixture
  6. filtrationfiltered through a pad of diatomaceous earth
  7. customThe filtrate was collected
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude reaction mixture
  11. customwas then purified by column chromatography (silica gel; DCM to DCM/EtOAc up to 6% as eluent)
  12. customThe desired fractions were collected
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-be239f504d234da3a9080054c56fb0f0
Source dataset
uspto-grants-2015_08
Patent number
US09114138B2

Reaction notes

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