Citric Acid → HCID 11847282, compound

HRID 1158856Notes

Reaction equation

HRID 1158856 reaction equation
[N:1]1[C:2]([CH:10]=[O:11])=[CH:3][N:4]2[CH2:9][CH2:8][S:7][CH2:6][C:5]=12.[Mg+2].[Br-].[Br-].[N+:15]([C:18]1[CH:36]=[CH:35][C:21]([CH2:22][O:23][C:24]([C:26]2[N:27]3[C@H:30]([S:31][CH:32]=2)[C@@H:29]([Br:33])[C:28]3=[O:34])=[O:25])=[CH:20][CH:19]=1)([O-:17])=[O:16].[C:37](OC(=O)C)(=[O:39])[CH3:38].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C1C=CN=CC=1.C(N(CC)CC)C.C1COCC1.C(#N)C>[N+:15]([C:18]1[CH:36]=[CH:35][C:21]([CH2:22][O:23][C:24]([C:26]2[N:27]3[C@H:30]([S:31][CH:32]=2)[C:29]([CH:10]([O:11][C:37](=[O:39])[CH3:38])[C:2]2[N:1]=[C:5]4[N:4]([CH:3]=2)[CH2:9][CH2:8][S:7][CH2:6]4)([Br:33])[C:28]3=[O:34])=[O:25])=[CH:20][CH:19]=1)([O-:17])=[O:16]

Participants

10

Reactant 5

HCID 311Citric AcidHCID 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 118471325,6-DIHYDRO-8H-IMIDAZO[2,1-C][1,4]THIAZINE-2-CARBALDEHYDE

Product 1

HCID 11847282HCID 11847282, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

The dry acetonitrile (20 mL) solution of 5,6-dihydro-8H-imidazo[2,1-c][1,4]thiazine-2-carbaldehyde (392 mg) was added to the dry acetonitrile (20 mL) solution of MgBr2 (1.1 g) under a nitrogen atmosphere at room temperature then the mixture was stirred for 10 min. The dry THF (40 mL) solution 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 (1.0 g) was added and the mixture was cooled to −20° C. then triethylamine (0.8 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 3.5 h at −20° C. and treated with 4-dimethylamino pyridine (30 mg) and acetic anhydride (0.44 mL) in one portion. The reaction mixture was warmed to 0° C. and stirred for 14 h at 0° C. 10% Citric acid aqueous solution (240 mL) was added to the reaction mixture and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with water, saturated sodium hydrogen carbonate and brine, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was roughly purified by silica gel column chromatography, eluted with CH2Cl2-acetone (50:1), and crude (5R)-6-[acetoxy-(5,6-dihydro-8H-imidazo[2,1-c][1,4]thiazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester was obtained as solid.

Workup

  1. stirringThe reaction mixture was stirred for 3.5 h at −20° C.
  2. temperatureThe reaction mixture was warmed to 0° C.
  3. stirringstirred for 14 h at 0° C
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  5. washThe combined organic layer was washed with water, saturated sodium hydrogen carbonate and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe residue was roughly purified by silica gel column chromatography
  10. washeluted with CH2Cl2-acetone (50:1)

Sources & evidence

ORD record
ord-5fce02f6a2b845e8b72d7f241e4b8b9f
Source dataset
uspto-grants-2010_10
Patent number
US07812014B2

Reaction notes

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