Potassium Carbonate → HCID 58103887, compound

HRID 1627027Notes

Reaction equation

HRID 1627027 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:29]([O:36][C:37]1[C:42]([F:43])=[CH:41][CH:40]=[CH:39][C:38]=1Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>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:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:38]2[CH:39]=[CH:40][CH:41]=[C:42]([F:43])[C:37]=2[O:36][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

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 57535156HCID 57535156, compound

Product 1

HCID 58103887HCID 58103887, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
150 °C

Procedure

To a solution of 1,2,3,6-tetrahydro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridine-1-carboxylic acid ter-butylester (0.75 g, 2.426 mmol) [CAS 375853-82-0] (synthesis described in WO 2004072025 A2 20040826) in 1,4-dioxane (7 ml) and an aqueous saturated solution of K2CO3 (3.5 ml), was added 2-benzyloxy-1-bromo-3-fluoro-benzene (1.023 mg, 3.638 mmol) [1036724-55-6]. The resulting solution was degassed using a stream of nitrogen and to this was added Pd(PPh3)4 (0.14 g, 0.121 mmol). The reaction was then subjected to microwave heating in a sealed tube at 150° C. for 10 min. After cooling to room temperature, the reaction mixture was diluted with water and washed with EtOAc. The organic layer was separated, dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography (silica gel; starting from Heptane/DCM up to 100% as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate compound D51 (0.727 g, 78%)

Workup

  1. customThe resulting solution was degassed
  2. temperatureAfter cooling to room temperature
  3. washwashed with EtOAc
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography (silica gel
  8. customThe desired fractions were collected
  9. customevaporated in vacuo
  10. customto yield intermediate compound D51 (0.727 g, 78%)

Sources & evidence

ORD record
ord-5b600c6e3da7489fa85a9ef4fe143cad
Source dataset
uspto-grants-2014_07
Patent number
US08785486B2

Reaction notes

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