Hydrochloric Acid → (1-(1-Methylpiperidin-4-yl)-1H-pyrazol-4-yl)boronic acid pinacol ester

HRID 1404297Notes

Reaction equation

HRID 1404297 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([B:19]3[O:23][C:22]([CH3:25])([CH3:24])[C:21]([CH3:27])([CH3:26])[O:20]3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(N(CC)CC)C.IC>O1CCOCC1>[CH3:6][N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([B:19]3[O:23][C:22]([CH3:25])([CH3:24])[C:21]([CH3:27])([CH3:26])[O:20]3)[CH:16]=[N:15]2)[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 8471TriethylamineHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

Product 1

HCID 59231689(1-(1-Methylpiperidin-4-yl)-1H-pyrazol-4-yl)boronic acid pinacol ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 5.00 g (13.3 mmol) 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester in a 4 N solution of hydrochloric acid in dioxane was stirred at room temperature for 16 hours. The precipitate that has formed was filtered off and the filtrate was evaporated to dryness. This residue was dissolved in 20 ml DMF and 2.6 ml (18.5 mmol) triethylamine and 0.6 ml (9.7 mmol) iodomethane were added. The reaction mixture was stirred for 16 hours at room temperature. The precipitate that had formed was filtered off and the filtrate was evaporated in vacuo. The residue was partitioned between water and dichloromethane. The organic phase was dried over sodium sulphate and evaporated. The residue was chromatographed on a silica gel column with toluene/ethylacetate as eluent yielding 1-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine as colourless crystals; HPLC-MS: 1.29 min, [M+H] 292.

Workup

  1. customThe precipitate that has formed
  2. filtrationwas filtered off
  3. customthe filtrate was evaporated to dryness
  4. dissolutionThis residue was dissolved in 20 ml DMF
  5. customThe precipitate that had formed
  6. filtrationwas filtered off
  7. customthe filtrate was evaporated in vacuo
  8. customThe residue was partitioned between water and dichloromethane
  9. dry with materialThe organic phase was dried over sodium sulphate
  10. customevaporated
  11. customThe residue was chromatographed on a silica gel column with toluene/ethylacetate as eluent

Sources & evidence

ORD record
ord-507079c8f6e74b8e96dc4aa55d1481a5
Source dataset
uspto-grants-2014_12
Patent number
US08912216B2

Reaction notes

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