Acetic Anhydride → HCID 86607969, compound

HRID 1158893Notes

Reaction equation

HRID 1158893 reaction equation
[N+:1]([C:4]1[CH:24]=[CH:23][C:7]([CH2:8][O:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]3[N:18]=[C:19]([CH:21]=[O:22])[CH:20]=[C:14]3[CH2:13]2)=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[Mg+2].[Br-].[Br-].[N+:28]([C:31]1[CH:49]=[CH:48][C:34]([CH2:35][O:36][C:37]([C:39]2[N:40]3[C@H:43]([S:44][CH:45]=2)[C@@H:42]([Br:46])[C:41]3=[O:47])=[O:38])=[CH:33][CH:32]=1)([O-:30])=[O:29].[C:50](OC(=O)C)(=[O:52])[CH3:51]>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.CCN(CC)CC.C1COCC1.C(#N)C>[N+:1]([C:4]1[CH:24]=[CH:23][C:7]([CH2:8][O:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]3[N:18]=[C:19]([CH:21]([O:22][C:50](=[O:52])[CH3:51])[C:42]4([Br:46])[C:41](=[O:47])[N:40]5[C@@H:43]4[S:44][CH:45]=[C:39]5[C:37]([O:36][CH2:35][C:34]4[CH:48]=[CH:49][C:31]([N+:28]([O-:30])=[O:29])=[CH:32][CH:33]=4)=[O:38])[CH:20]=[C:14]3[CH2:13]2)=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

10

Reactant 4

HCID 7918Acetic Anhydride2×HCID 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 11847134HCID 11847134, compound

Product 1

HCID 86607969HCID 86607969, compound

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

2-Formyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine-5-carboxylic acid 4-nitrobenzyl ester (2.71 g) was added to the dry acetonitrile (164 mL) solution of anhydrous MgBr2 (cont. 98%) (6.17 g) under a nitrogen atmosphere at room temperature. The dry THF solution (164 mL) of (5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl ester (cont. 96.5%) (3.27 g) was added to the mixture, cooled to −20° C., and Et3N (cont. 99%) (9.24 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 1.5 h at −20° C. and treated with acetic anhydride (cont. 97%) (3.19 mL) and DMAP (cont. 99%) (203 mg) in one portion. The reaction mixture was warmed to 0° C. and stirred for 1 h at 0° C. Acetic anhydride (3.19 mL) was added to the solution and stirred for 15 h at 0° C. The mixture was diluted with ethyl acetate and washed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, water and brine. The organic layer was dried (MgSO4), followed by concentration under reduced pressure. The residue was purified with silica-gel column chromatography three times (n-hexane-AcOEt (1/1 to 2/3), CHCl3-acetone (29/1 to 19/1) and CHCl3-acetone (29/1)). The titled compound was obtained as yellow amorphous (diastereo-mixture (64:36), 3.30 g, 53%).

Workup

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 1 h at 0° C
  3. stirringstirred for 15 h at 0° C
  4. washwashed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, water and brine
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationfollowed by concentration under reduced pressure
  7. customThe residue was purified with silica-gel column chromatography three times (n-hexane-AcOEt (1/1 to 2/3), CHCl3-acetone (29/1 to 19/1) and CHCl3-acetone (29/1))

Sources & evidence

ORD record
ord-8d4adb2d5aa848c5990ea34162a84507
Source dataset
uspto-grants-2010_10
Patent number
US07812014B2

Reaction notes

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