tert-Butyl hydroperoxide → Benzyl ((S)-3-(4-((tert-butyloxycarbonylamino)methyl)phenyl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)carbamate

HRID 1912360Notes

Reaction equation

HRID 1912360 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C@H:17]([NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@H:18]([OH:22])[C:19]([CH3:21])=[CH2:20])=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O:38]O)(C)(C)C.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl.C/C(/O)=C\C(C)=O.C/C(/O)=C\C(C)=O.O=[V].CCOC(C)=O>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C@H:17]([NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:18]([C@@:19]2([CH3:21])[CH2:20][O:38]2)=[O:22])=[CH:12][CH:11]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 6410tert-Butyl hydroperoxideHCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 71562124Benzyl ((2S,3R)-1-(4-((tert-butyloxycarbonylamino)methyl)phenyl)-3-hydroxy-4-methylpent-4-en-2-yl)carbamate

Product 1

HCID 71562239Benzyl ((S)-3-(4-((tert-butyloxycarbonylamino)methyl)phenyl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)carbamate

Reagents, catalysts & solvents 3

HCID 16217092Bis(2,4-pentanedionato)vanadium(IV) OxideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Allylic alcohol 13 (1.79 g, 3.94 mmol) was dissolved in DCM (25 mL) and cooled to 0° C. after which vanadyl acetylacetonate (0.1 eq., 0.4 mmol, 107 mg) and tBuOOH (3 eq., 12.0 mmol, 2.18 mL; 5.5 M in decane) were added and the mixture was stirred at 0° C. until TLC analysis indicated complete consumption of starting material after 2 hours. The mixture was concentrated under reduced pressure, redissolved in EtOAc and extracted with half sat. aq. NaHCO3, H2O and brine, dried over MgSO4 and concentrated under reduced pressure. The resulting product was quickly purified by column chromatography (20%->60% EtOAc/PE) and immediately subjected to the next step because of the possible instability of the intermediate. The compound was dissolved in DCM (25 mL) and Dess-Martin periodinane (3 eq., 11.0 mmol, 4.50 g) was added. The mixture was stirred at room temperature for 12 hours after which TLC analysis indicated complete conversion. Next, a 1:4 (v/v) mixture (150 mL) of NaHCO3 (sat. aq.)/Na2S2O3 (1 M aq.) and the resulting emulsion was stirred vigorously for 30 minutes after which the layers were separated and the aqueous layer extracted with DCM. The combined organic layers were extracted with sat. aq. NaHCO3, dried over MgSO4 and concentrated under reduced pressure. The title compound was obtained after column chromatography (20%->30% EtOAc/PE) as a colourless oil (yield: 1.03 g, 2.20 mmol, 56%). 1H NMR (400 MHz, CDCl3): δ=7.33-7.22 (m, 5H), 7.16 (d, J=7.94 Hz, 2H), 7.08 (d, J=7.95 Hz, 2H), 5.51 (d, J=8.19 Hz, 1H), 5.06-5.01 (m, 1H), 4.97 (d, J=4.39 Hz, 2H), 4.60 (dd, J=12.65, 7.86 Hz, 1H), 4.24 (d, J=4.36 Hz, 2H), 3.26 (d, J=4.62 Hz, 1H), 3.08 (dd, J=13.96, 4.48 Hz, 1H), 2.87 (d, J=4.53 Hz, 1H), 2.70 (dd, J=13.88, 8.12 Hz, 1H), 1.49 (s, 3H), 1.44 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ=207.77, 155.74, 155.66, 137.61, 135.97, 134.62, 129.32, 128.26, 127.91, 127.76, 127.44, 79.15, 66.62, 58.99, 54.07, 52.12, 44.07, 36.61, 28.21, 16.34 ppm. [α]D23=+82.2 (c=1, CHCl3).

Workup

  1. additionwere added
  2. customconsumption of starting material after 2 hours
  3. concentrationThe mixture was concentrated under reduced pressure
  4. dissolutionredissolved in EtOAc
  5. extractionextracted with half sat. aq. NaHCO3, H2O and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting product was quickly purified by column chromatography (20%->60% EtOAc/PE)
  9. dissolutionThe compound was dissolved in DCM (25 mL)
  10. stirringThe mixture was stirred at room temperature for 12 hours after which TLC analysis
  11. customwere separated
  12. extractionthe aqueous layer extracted with DCM
  13. extractionThe combined organic layers were extracted with sat. aq. NaHCO3
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2e900de3d18e44d3862179fcd78aa4fd
Source dataset
uspto-grants-2013_12
Patent number
US08609610B2

Reaction notes

Loading…