Acetic Anhydride → HCID 68686254, compound

HRID 1158886Notes

Reaction equation

HRID 1158886 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH:14]=[C:15]([CH:17]=[O:18])[N:16]=[C:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Mg+2].[Br-].[Br-].[N+:22]([C:25]1[CH:43]=[CH:42][C:28]([CH2:29][O:30][C:31]([C:33]2[N:34]3[C@H:37]([S:38][CH:39]=2)[C@@H:36]([Br:40])[C:35]3=[O:41])=[O:32])=[CH:27][CH:26]=1)([O-:24])=[O:23].[C:44](OC(=O)C)(=[O:46])[CH3:45]>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.CCN(CC)CC.C1COCC1.C(#N)C>[N+:22]([C:25]1[CH:43]=[CH:42][C:28]([CH2:29][O:30][C:31]([C:33]2[N:34]3[C@H:37]([S:38][CH:39]=2)[C:36]([CH:17]([O:18][C:44](=[O:46])[CH3:45])[C:15]2[N:16]=[C:10]4[CH2:9][N:8]([CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[CH2:13][CH2:12][N:11]4[CH:14]=2)([Br:40])[C:35]3=[O:41])=[O:32])=[CH:27][CH:26]=1)([O-:24])=[O:23]

Participants

10

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 21941423HCID 21941423, compound

Product 1

HCID 68686254HCID 68686254, compound

Reagents, catalysts & solvents 5

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

Conditions

Temperature
-20 °C

Procedure

7-Benzyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde (139 mg) was added to the dry acetonitrile (8.7 mL) solution of anhydrous MgBr2 (325 mg) under a nitrogen atmosphere at room temperature. The dry THF solution (8.7 mL) of (5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (223 mg) was added to the mixture, cooled to −20° C., and Et3N (0.24 mL) was added in one portion. The reaction vessel was covered with foil to exclude light. The reaction mixture was stirred for 5 h at −20° C. and treated with acetic anhydride (0.11 mL) and DMAP (7 mg) in one portion. The reaction mixture was warmed to 0° C. 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) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then the column was eluted with n-hexane—AcOEt (3/1˜1/1). The titled compound was obtained as two diastereo mixture (80/20, purple amorphous solid, 233 mg, 61%).

Workup

  1. temperatureThe reaction mixture was warmed to 0° C.
  2. stirringstirred for 15 h at 0° C
  3. washwashed with 5% citric acid aqueous solution, saturated sodium hydrogen carbonate, water and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. washthe column was eluted with n-hexane—AcOEt (3/1˜1/1)

Sources & evidence

ORD record
ord-686bd11fa48e4eb3a2e406d14dc45369
Source dataset
uspto-grants-2010_10
Patent number
US07812014B2

Reaction notes

Loading…