Ethyl Acetate → 2-Acetamido-N-(tert-butyl)-2-(piperidin-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamide

HRID 579605Notes

Reaction equation

HRID 579605 reaction equation
[C:1]([NH:4][C:5]([CH:26]1[CH2:31][CH2:30][N:29](C(OCC2C=CC=CC=2)=O)[CH2:28][CH2:27]1)([CH2:13][CH2:14][CH2:15][CH2:16][B:17]1[O:21][C:20]([CH3:23])([CH3:22])[C:19]([CH3:25])([CH3:24])[O:18]1)[C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])(=[O:3])[CH3:2].C(OCC)(=O)C>CO.CCCCCCC.[Pd]>[C:1]([NH:4][C:5]([CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH2:13][CH2:14][CH2:15][CH2:16][B:17]1[O:18][C:19]([CH3:24])([CH3:25])[C:20]([CH3:23])([CH3:22])[O:21]1)[C:6]([NH:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7])(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 8857Ethyl AcetateHCID 66832700HCID 66832700, compound

Product 1

HCID 668337692-Acetamido-N-(tert-butyl)-2-(piperidin-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamideYield 96%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8900HeptaneSolvent

Procedure

In a 100 mL round bottom flask while under an argon atmosphere, benzyl 4-(2-acetamido-1-(tert-butylamino)-1-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-yl)piperidine-1-carboxylate (3.0 g, 5.25 mmol) in methanol (40 mL) was degassed with argon (bubbled through solution) and subsequently treated with palladium (25 mg, 10 wt % on active carbon, wet, Degussa type E101 NE/W). After continued bubbling for 10 min the argon was replaced with a slow stream of hydrogen. After 1.5 h the reaction was complete (reaction monitored by TLC for the disappearance of starting material (50% ethyl acetate in heptane, Rf 0.3) and solution was purged with argon, filtered through the Celite 545 and the filter cake washed with methanol. The methanol solution was concentrated and collected solvents evaporated to give crude 2-acetamido-N-tert-butyl-2-(piperidin-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamide (2.20 g 96%) which was used without further purification (contained approximately 10% product with loss of boronic acid protecting group). 1H NMR (CDCl3, 300 MHz) δ 6.95 (s, 1H), 5.53 (s, 1H), 3.09 (bt, J=11.1 Hz, 2H), 2.80 (ddd, J1=14.1 Hz, J2=13.5 Hz, J3=4.5 Hz, 1H), 2.65-2.48 (m, 2H), 2.26 (dddd, J1=12.0 Hz, J2=12.0 Hz, J3=3.0 Hz, J4=2.7 Hz, 1H), 2.00-1.90 (m, 1H), 1.98 (s, 3H), 1.78-1.63 (m, 2H), 1.45-1.00 (m, 5H), 1.36 (s, 9H), 1.21 (s, 8H), 0.73 (t, J=7.5 Hz, 2H).

Workup

  1. customAfter continued bubbling for 10 min the argon
  2. custom(reaction
  3. customwas purged with argon
  4. filtrationfiltered through the Celite 545
  5. washthe filter cake washed with methanol
  6. concentrationThe methanol solution was concentrated
  7. customcollected solvents
  8. customevaporated

Sources & evidence

ORD record
ord-ebac9a92c3ae4a05bf7c33b4313dbbc1
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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