Acetic Anhydride → (5R, 6RS)-6-{(RS)-Acetoxy-[4,5,6,7-tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-2-yl]-methyl}-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl Ester

HRID 1744933Notes

Reaction equation

HRID 1744933 reaction equation
[N:1]1[C:2]([CH:13]=[O:14])=[CH:3][N:4]2[N:12]3[C:7]([CH2:8][CH2:9][CH2:10][CH2:11]3)=[N:6][C:5]=12.[Mg+2].[Br-].[Br-].[N+:18]([C:21]1[CH:39]=[CH:38][C:24]([CH2:25][O:26][C:27]([C:29]2[N:30]3[C@H:33]([S:34][CH:35]=2)[C@@H:32]([Br:36])[C:31]3=[O:37])=[O:28])=[CH:23][CH:22]=1)([O-:20])=[O:19].[C:40](OC(=O)C)(=[O:42])[CH3:41]>C(OCC)(=O)C.C(N(CC)CC)C.C1COCC1.C(#N)C>[N+:18]([C:21]1[CH:39]=[CH:38][C:24]([CH2:25][O:26][C:27]([C:29]2[N:30]3[C@H:33]([S:34][CH:35]=2)[C:32]([CH:13]([O:14][C:40](=[O:42])[CH3:41])[C:2]2[N:1]=[C:5]4[N:6]=[C:7]5[N:12]([CH2:11][CH2:10][CH2:9][CH2:8]5)[N:4]4[CH:3]=2)([Br:36])[C:31]3=[O:37])=[O:28])=[CH:23][CH:22]=1)([O-:20])=[O:19]

Participants

9

Reactant 4

HCID 7918Acetic AnhydrideHCID 82241Magnesium BromideHCID 11280588(5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl esterHCID 222244644,5,6,7-Tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-2-carbaldehyde

Product 1

HCID 68701663(5R, 6RS)-6-{(RS)-Acetoxy-[4,5,6,7-tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-2-yl]-methyl}-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl Ester

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

4,5,6,7-Tetrahydro-1,3a,3b,8-tetraaza-cyclopenta[a]indene-2-carbaldehyde (2.97 g) was added to the dry acetonitrile (110 mL) solution of anhydrous MgBr2 (4.45 g) under a nitrogen atmosphere at room temperature. The dry THF solution (110 mL) of (5R, 6S)-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (2.97 g) was added to the reaction mixture, cooled to −20° C., and triethylamine (6.45 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. After the mixture was stirred for 1.2 h at −20° C., acetic anhydride (2.9 mL) was added in one portion. The reaction mixture was warmed to 0° C. and stirred for 16.5 h at 0° C. The mixture was diluted with ethyl acetate and washed with H2O and brine. The organic layer was dried (MgSO4) and filtered through a pad of Celite. The pad was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, eluted with ethyl acetate—n-hexane (3/1) and then with ethyl acetate—methanol (5/1). The title compound was obtained as a brown amorphous solid (651.6 mg, 13%). 1H-NMR (400 MHz, CDCl3) δ 2.10–2.24 (m, 4H), 2.29 (s, 3H), 3.04–3.07 (m, 2H), 4.28–4.32 (m, 2H), 5.27 (d, 1H, J=13.7 Hz), 5.43 (d, 1H, J=13.7 Hz), 6.19 (s, 1H), 6.91 (s, 1H), 7.01 (s, 1H), 7.49 (s, 1H), 7.59–7.62 (m, 2H), 8.23–8.25 (m, 2H).

Workup

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 16.5 h at 0° C
  3. washwashed with H2O and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered through a pad of Celite
  6. washThe pad was washed with ethyl acetate
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. washeluted with ethyl acetate—n-hexane (3/1)

Sources & evidence

ORD record
ord-955f780fa6d44ad88bf7c97bebd4880e
Source dataset
uspto-grants-2006_03
Patent number
US07018997B2

Reaction notes

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