Tributylphosphine → 1,1-Dimethylethyl 4-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]methyl]-1-piperidinecarboxylate

HRID 1775010Notes

Reaction equation

HRID 1775010 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[CH3:19][C:20]1([CH3:32])[C:24]([CH3:26])([CH3:25])[O:23][B:22]([C:27]2[CH:28]=[N:29][NH:30][CH:31]=2)[O:21]1.O[CH2:34][CH:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]1.C(P(CCCC)CCCC)CCC>C1COCC1>[CH3:19][C:20]1([CH3:32])[C:24]([CH3:25])([CH3:26])[O:23][B:22]([C:27]2[CH:31]=[N:30][N:29]([CH2:34][CH:35]3[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:45])([CH3:47])[CH3:46])=[O:42])[CH2:37][CH2:36]3)[CH:28]=2)[O:21]1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 593926251,1-Dimethylethyl 4-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]methyl]-1-piperidinecarboxylateYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 630.8 mg (2.5 mmol) of 1,1′-(azodicarbonyl)-dipiperidine in 5 ml of THF was added dropwise to a mixture of 388 mg (2.0 mmol) of 4,4,5,5-Tetramethyl-2-(1H-pyrazol-4-yl)-1,3,2-dioxaborolane, 538 mg (2.5 mmol) of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate and 0.62 ml (2.5 mmol) of tributylphosphine in 6 ml of tetrahydrofuran at 0° C. The mixture was stirred for 18 hours. The precipitate was filtered out and washed with ethyl ether. The filtrate was mixed with 50 ml of water and extracted with ethyl ether. The organic layer was washed with water, brine, dried over MgSO4 and concentrated. The residue was purified on 24 g silica column eluting with MeOH 0-4% gradient in DCM to afford 0.43 g (55%) of tert-Butyl 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate. ESI MS m/z 392.1

Workup

  1. filtrationThe precipitate was filtered out
  2. washwashed with ethyl ether
  3. additionThe filtrate was mixed with 50 ml of water
  4. extractionextracted with ethyl ether
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified on 24 g silica column
  9. washeluting with MeOH 0-4% gradient in DCM

Sources & evidence

ORD record
ord-a02dd9250b434c63a5fdfcc8121698b3
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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