Hydrochloric Acid → 1-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropan-1-amine

HRID 1509325Notes

Reaction equation

HRID 1509325 reaction equation
[CH3:1][C:2]1([CH3:17])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[O:3]1.[CH2:18]([Mg]Br)[CH3:19].B(F)(F)F.CCOCC.Cl.[OH-].[Na+]>O1CCCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:8][C:6]1([CH3:7])[C:2]([CH3:17])([CH3:1])[O:3][B:4]([C:9]2[CH:16]=[CH:15][C:12]([C:13]3([NH2:14])[CH2:19][CH2:18]3)=[CH:11][CH:10]=2)[O:5]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 27346254-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 467396631-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropan-1-amineYield 12.4%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

In a 40 mL reaction tube was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (500 mg, 2.18 mmol) and titanium(IV) isopropoxide (710 μl, 2.40 mmol) in anhydrous tetrahydrofuran (11 ml) to give a colourless solution. The reaction mixture was cooled to −70° C. under a nitrogen atmosphere, followed by the dropwise addition of ethylmagnesium bromide (1M in THF, 4.80 ml, 4.80 mmol) over a period of 30 minutes. The resulting orange solution was stirred at −78° C. for 10 minutes, followed by warming to room temperature and stirring for 60 minutes. After this period, boron trifluoride diethyl etherate (540 μl, 4.37 mmol) was added and the mixture stirred at room temperature for 60 minutes. To the reaction was then added 1M HCl solution (6 ml) and stirred for 15 minutes before basification with 2M NaOH solution. The organic phase was separated and the aqueous washed with ethyl acetate (3×4 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 0:100) to give the desired product as an off-white solid (70 mg, 12% yield). 1H-NMR (500 MHz, CDCl3) δ 7.76 (2H, d), 7.29 (2H, d), 2.32 (2H, br s), 1.34 (12H, s), 1.12 (2H, dd), 1.01 (2H, dd). LCMS RT=0.68 min, M+H+=260.20.

Workup

  1. customIn a 40 mL reaction tube
  2. customto give a colourless solution
  3. temperatureby warming to room temperature
  4. stirringstirring for 60 minutes
  5. waitAfter this period
  6. stirringthe mixture stirred at room temperature for 60 minutes
  7. customThe organic phase was separated
  8. washthe aqueous washed with ethyl acetate (3×4 mL)
  9. dry with materialThe combined organic phases were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure
  12. customThe residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 0:100)

Sources & evidence

ORD record
ord-d72dea83a7ac4831a9a2ba2e89ada4bb
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

Loading…