1,8-Diazabicyclo(5.4.0)undec-7-ene → tert-butyl 3-(cyanomethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate

HRID 1852949Notes

Reaction equation

HRID 1852949 reaction equation
[C:1]([CH:3]=[C:4]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1)#[N:2].[CH3:15][C:16]1([CH3:28])[C:20]([CH3:22])([CH3:21])[O:19][B:18]([C:23]2[CH:24]=[N:25][NH:26][CH:27]=2)[O:17]1.C1CCN2C(=NCCC2)CC1>C(#N)C>[C:1]([CH2:3][C:4]1([N:26]2[CH:27]=[C:23]([B:18]3[O:17][C:16]([CH3:28])([CH3:15])[C:20]([CH3:22])([CH3:21])[O:19]3)[CH:24]=[N:25]2)[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1)#[N:2]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 457892161-(tert-Butoxycarbonyl)-3-(cyanomethylene)azetidine

Product 1

HCID 67457197tert-butyl 3-(cyanomethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylateYield 64.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a 5 L flask, tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (Preparation F, Step A; 94.2 g, 485 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (85.6 g, 441 mmol) were dissolved in acetonitrile (882 mL). To this was then added DBU (33.0 mL, 220 mmol). The resulting clear orange brown mixture was stirred at ambient temperature for 15 hours. The reaction mixture was concentrated down to remove solvents and afforded a dark reddish-orange oil. Solid crystals formed within a few hours at ambient temperature. This was isolated by washing with cold Et2O and cold EtOAc (carefully to prevent dissolution) to afford 110 g (64% yield) of the title compound. The recrystallization was repeated to give another 13.7 g (8% yield). Additional compound was isolated by purification of the filtrate from the above recrystallization. This was purified by silica chromatography eluting with a 20-50% EtOAc/Hexanes gradient to afford an additional 22.7 g (13%) of the title compound. MS (apci) m/z=289.2 (M+H-Boc).

Workup

  1. concentrationThe reaction mixture was concentrated down
  2. customto remove solvents
  3. customafforded a dark reddish-orange oil
  4. customSolid crystals formed within a few hours at ambient temperature
  5. customThis was isolated
  6. washby washing with cold Et2O and cold EtOAc (carefully
  7. dissolutiondissolution)

Sources & evidence

ORD record
ord-5c78389f53344954a289dd82bd5a9a4f
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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