Water → tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

HRID 1672436Notes

Reaction equation

HRID 1672436 reaction equation
BrC1[CH:3]=[C:4]2[C:9](=[CH:10]C=1)[CH:8]=NC=[CH:5]2.O.[C:13]([O-:16])([O-])=[O:14].[Cs+].[Cs+].[BH:19]([OH:21])[OH:20].[NH:22]1[CH:26]=[CH:25][CH:24]=[N:23]1>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:13]([N:22]1[CH:26]=[C:25]([B:19]2[O:21][C:9]([CH3:8])([CH3:10])[C:4]([CH3:3])([CH3:5])[O:20]2)[CH:24]=[N:23]1)([O:16][C:4]([CH3:9])([CH3:5])[CH3:3])=[O:14]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 3136816-BromoisoquinolineHCID 178514841HCID 178514841, compound

Product 1

HCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
84 °C

Procedure

An alternative procedure for the preparation is as follows: To a 3-necked flask equipped with stirrer, nitrogen inlet and internal thermometer was charged with 3-amino, 6-bromoisoquinoline (6.0 g, 20.0 mmol), 2-(2′,6′-dimethoxybiphenyl)dicyclohexylphosphine (S-Phos) (2.0 g 3.0 mmol), thoroughly freshly degassed DME (200 mL), water (40 mL), and Cs2CO3 (46.2 g, 142.0 mmol). The suspension was placed under nitrogen in a pre-heated oil bath at 86° C. Meanwhile, a solution of 1-BOC-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (10.8 g, 36.0 mmol) in degassed DME (30 mL) was prepared and stored under nitrogen. When the internal temperature of the suspension had reached 84° C., the Pd2(dba)3 (2.8 g, 3.0 mmol) was added, and quickly followed by dropwise addition of the pyrazole boronate solution (via syringe over 5 min). The resulting bi-phasic dark orange solution was stirred at 84° C. for 20 mins. The flask was then placed in an ice bath to cool rapidly. Once at ambient temperature, the mixture was filtered to remove inorganic substance, washed with water (2×25 mL). Upon reduction of the solution volume via evaporation the solid product was filtered and collected. The light yellow product was washed with ethyl ether 3 time (20 ml) to give a pale yellow solid product. Yield: 6.1 g, 98.4%.

Workup

  1. customTo a 3-necked flask equipped with stirrer, nitrogen inlet
  2. customThe suspension was placed under nitrogen in a pre-heated oil bath at 86° C
  3. customhad reached 84° C.
  4. customThe flask was then placed in an ice bath
  5. temperatureto cool rapidly
  6. filtrationOnce at ambient temperature, the mixture was filtered
  7. customto remove inorganic substance
  8. washwashed with water (2×25 mL)
  9. customUpon reduction of the solution volume via evaporation the solid product
  10. filtrationwas filtered
  11. customcollected
  12. washThe light yellow product was washed with ethyl ether 3 time (20 ml)
  13. customto give a pale yellow solid product

Sources & evidence

ORD record
ord-531f71dfcfd049d8851b2e447d946da0
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

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