Potassium Bromide → (1-benzylcyclobutyl)methyl(1S)-1-(oxo{[(1r)-1-phenylethyl]amino}acetyl)pentylcarbamate

HRID 1180738Notes

Reaction equation

HRID 1180738 reaction equation
[OH:1][CH:2]([C@@H:14]([NH:19][C:20](=[O:34])[O:21][CH2:22][C:23]1([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:26][CH2:25][CH2:24]1)[CH2:15][CH2:16][CH2:17][CH3:18])[C:3](=[O:13])[NH:4][C@@H:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6].[Br-].[K+].C(=O)(O)[O-].[Na+]>ClCCl>[O:13]=[C:3]([NH:4][C@@H:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6])[C:2]([C@@H:14]([NH:19][C:20](=[O:34])[O:21][CH2:22][C:23]1([CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:24][CH2:25][CH2:26]1)[CH2:15][CH2:16][CH2:17][CH3:18])=[O:1]

Participants

5

Reactant 3

HCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 58979674(1-benzylcyclobutyl)methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1r)-1-phenylethyl]amino}ethyl)pentylcarbamate

Product 1

HCID 10127748(1-benzylcyclobutyl)methyl(1S)-1-(oxo{[(1r)-1-phenylethyl]amino}acetyl)pentylcarbamateYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 240 mg (0.51 mmol) of (1-benzylcyclobutyl)methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate in 2 mL of dichloromethane at 0° C. was added 1 mg of 2,2,6,6-tetramethyl-1-piperidinyloxy free radical and 5 mg of potassium bromide. A solution of 30 mg of sodium bicarbonate in 2.5 mL of household bleach was added and the reaction stirred for 30 min. The reaction was extracted with ethyl acetate and and washed 0.5 N hydrochloric acid. The organic phase was washed with saturated sodium bicarbonate, washed with brine, dried over magnesium sulfate, and concentrated under vacuum. The product was purified by silica chromatography eluting with 2.5:7.5 acetone:hexanes to afford 128 mg (53%) of (1-benzylcyclobutyl)methyl(1S)-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate. M.P.=96-98° C. Elemental analysis: Theory; C=72.39%, H=7.81%, N=6.03%. Found; C=72.14%, H=7.81%, N=5.99%. 1H NMR (300 MHz, 80° C., DMSO-d6) δ 8.83 (d, J=8 Hz, 1H), 7.19-7.38 (m, 11H), 5.02 (qnt, J=7 Hz, 1H), 4.85 (m, 1H), 3.83 (s, 2H), 2.79 (s, 1H), 1.67-1.89 (m, 7H), 1.51-1.60 (m, 1H), 1.47 (d, J=7 Hz, 3H), 1.25-1.40 (m, 4H), 0.86 (t, J=7 Hz, 3H). ES-LCMS m/z 487 (M+Na). HRMS C28H36N2O4 m/z 487.2573 (M+Na)Cal; 487.2552 (M+Na)Obs.

Workup

  1. extractionThe reaction was extracted with ethyl acetate
  2. washwashed 0.5 N hydrochloric acid
  3. washThe organic phase was washed with saturated sodium bicarbonate
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe product was purified by silica chromatography
  8. washeluting with 2.5:7.5 acetone

Sources & evidence

ORD record
ord-9e83fecb9fe64af4b0ce8932963879bb
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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