Potassium Carbonate → HCID 57459615, compound

HRID 1428501Notes

Reaction equation

HRID 1428501 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[C:6]([F:10])[CH:5]=[CH:4][C:3]=1[F:11].CC1(C)C(C)(C)OB([C:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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:29]([O:28][C:26]([N:23]1[CH2:22][CH:21]=[C:20]([C:2]2[C:3]([F:11])=[CH:4][CH:5]=[C:6]([F:10])[C:7]=2[O:8][CH3:9])[CH2:25][CH2:24]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 509981342-Bromo-1,4-difluoro-3-methoxybenzene

Product 1

HCID 57459615HCID 57459615, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

2-Bromo-1,4-difluoro-3-methoxy-benzene (0.7 g, 3.139 mmol) [C.A.S. 1208076-11-2] was added to a stirred solution of 3,6-dihydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1(2H)-pyridinecarboxylic acid, 1,1-dimethylethyl ester (1.262 g, 4.08 mmol) [C.A.S. 286961-14-6], Pd(PPh3)4 (0.072 g, 0.062 mmol) and K2CO3 (3.5 ml, aqueous sat. solution) in 1,4-dioxane (7 ml). The reaction mixture was heated at 150° C. under microwave irradiation for 10 min. After cooling, the mixture was diluted with water and extracted with Et2O. The organic phase was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/EtOAc 90/10 to 80/2 as eluent). The desired fractions were collected and concentrated in vacuo to give a residue that was triturated with Et2O to yield intermediate D52 (0.233 g, 22%).

Workup

  1. temperatureAfter cooling
  2. extractionextracted with Et2O
  3. customThe organic phase was separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (silica gel; Heptane/EtOAc 90/10 to 80/2 as eluent)
  7. customThe desired fractions were collected
  8. concentrationconcentrated in vacuo
  9. customto give a residue that
  10. customwas triturated with Et2O
  11. customto yield intermediate D52 (0.233 g, 22%)

Sources & evidence

ORD record
ord-ad829cf91bcc4383aef1ae36080703d5
Source dataset
uspto-grants-2015_01
Patent number
US08937060B2

Reaction notes

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