Acetate → N-(t-butyldimethylsilyl)-4-[3-(p-nitrobenzyloxycarbonyl)-2-oxopropyl]-azetidin-2-one

HRID 1493486Notes

Reaction equation

HRID 1493486 reaction equation
N1C=CC=CC=1.[Si:7]([N:14]1[CH:17]([CH2:18][CH:19]([OH:34])[CH2:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])[CH2:16][C:15]1=[O:35])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].CC(O)C.C([O-])(=O)C>C(Cl)Cl.[O-2].[O-2].[O-2].[Cr+6]>[Si:7]([N:14]1[CH:17]([CH2:18][C:19](=[O:34])[CH2:20][C:21]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([N+:31]([O-:33])=[O:32])=[CH:29][CH:30]=2)=[O:22])[CH2:16][C:15]1=[O:35])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 175AcetateHCID 1049PyridineHCID 3776IsopropanolHCID 12848994N-(t-butyldimethylsilyl)-4-[3-(p-nitrobenzyloxycarbonyl)-2-hydroxypropyl]-azetidin-2-one

Product 1

HCID 12804721N-(t-butyldimethylsilyl)-4-[3-(p-nitrobenzyloxycarbonyl)-2-oxopropyl]-azetidin-2-oneYield 58.3%

Reagents, catalysts & solvents 2

HCID 10219390chromium (VI) trioxideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Anyhdrous chromium trioxide (16.88 g 169 mmol) is added to a solution of anhydrous pyridine (27.3 ml, 338 mmol) in anhydrous methylene chloride (470 ml). The resulting mixture is stirred at room temperature for 30 minutes and then treated with a solution of N-(t-butyldimethylsilyl)-4-[3-(p-nitrobenzyloxycarbonyl)-2-hydroxypropyl]-azetidin-2-one (8.92 g, 21.1 mmol) in methylene chloride (80 ml). The reaction mixture is stirred an additional 15 minutes at room temperature and then treated with 2-propanol (6.75 ml). The methylene chloride phase is decanted from the dark, tary residue and evaporated under vacuum. The residue from this operation is triturated with diethyl ether (350 ml) and filtered through a pad of magnesium sulfate which is washed with additional ether (150 ml). The ethereal filtrate is washed with water (200 ml), 5% aqueous sodium bicarbonate (200 ml) and brine, dried with magnesium sulfate, filtered, evaporated under vacuum, and stripped with toluene to afford the crude product (5.99 g) as an amber oil. Chromatigraphy on a silica gel column using 3:2 petroleum etherethyl acetate as eluting solvent yields N-(t-butyldimethylsilyl)-4-[3-(p-nitrobenzyloxycarbonyl)-2-oxopropyl]-azetidin-2-one (5.17 g, 58%) as a pale yellow, viscous oil which solidifies. Trituration with diethyl ether gives the product as small, white crystals: mp 65°-66.5°, IR (CH2CL2) 1732, 1522, and 1350 cm) NMR (CDCl3) 8 0.20 (s,3,CH3), 0.23 (s,3,CH3), 0.93 (s,9,C(CH3)3), 2.58 (dd,1,J=2.7 and 15.7,H3β), 2.72 (dd,1,J=9.4 and 18.2, CH2COCH2CO2), 3.19 (dd,1,J=4.0 and 18.2, CH2COCH2CO2), 3.35 (dd,1,J=5.3 and 15.7,H3α), 3.55 (s,2,COCH2CO2), 3.90 (m,1,H4), 5.30 (s,2,CH2Ar), 7.55 and 8.25 (two d15,4,J-8.5,ArH); MS m/e 405 (M+ -15), 363 (M+ -57), 321 (363-42) and 136.

Workup

  1. stirringThe reaction mixture is stirred an additional 15 minutes at room temperature
  2. customThe methylene chloride phase is decanted from the dark, tary residue
  3. customevaporated under vacuum
  4. customThe residue from this operation is triturated with diethyl ether (350 ml)
  5. filtrationfiltered through a pad of magnesium sulfate which
  6. washis washed with additional ether (150 ml)
  7. washThe ethereal filtrate is washed with water (200 ml), 5% aqueous sodium bicarbonate (200 ml) and brine
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. customevaporated under vacuum
  11. customto afford the crude product (5.99 g) as an amber oil
  12. washas eluting solvent

Sources & evidence

ORD record
ord-16e0d8baba0b417a937033e94dffd39a
Source dataset
uspto-grants-1991_06
Patent number
US05021566

Reaction notes

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