Acetic Anhydride → 4-nitrobenzyl (5R)-6-[(acetyloxy)(3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazol-7-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

HRID 1744979Notes

Reaction equation

HRID 1744979 reaction equation
[S:1]1[C:13]2[N:5]([C:6]3[C:11]([N:12]=2)=[CH:10][CH:9]=[C:8]([CH:14]=[O:15])[CH:7]=3)[CH2:4][CH2:3][CH2:2]1.[Br-].[Mg+2].[Br-].[N+:19]([C:22]1[CH:40]=[CH:39][C:25]([CH2:26][O:27][C:28]([C:30]2[N:31]3[CH:34]([S:35][CH:36]=2)[CH:33]([Br:37])[C:32]3=[O:38])=[O:29])=[CH:24][CH:23]=1)([O-:21])=[O:20].[C:41](OC(=O)C)(=[O:43])[CH3:42]>C(OCC)(=O)C.C(N(CC)CC)C.C1COCC1.C(#N)C>[C:41]([O:15][CH:14]([C:8]1[CH:9]=[CH:10][C:11]2[N:12]=[C:13]3[S:1][CH2:2][CH2:3][CH2:4][N:5]3[C:6]=2[CH:7]=1)[C:33]1([Br:37])[C:32](=[O:38])[N:31]2[C@@H:34]1[S:35][CH:36]=[C:30]2[C:28]([O:27][CH2:26][C:25]1[CH:39]=[CH:40][C:22]([N+:19]([O-:21])=[O:20])=[CH:23][CH:24]=1)=[O:29])(=[O:43])[CH3:42]

Participants

9

Reactant 4

HCID 7918Acetic AnhydrideHCID 82241Magnesium BromideHCID 222244403,4-Dihydro-2H-1-thia-4a,9-diaza-fluorene-6-carbaldehydeHCID 684433356-Bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester

Product 1

HCID 696087324-nitrobenzyl (5R)-6-[(acetyloxy)(3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazol-7-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 36%

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

A 30 ml acetonitrile solution of 3,4-Dihydro-2H-1-thia-4a,9-diaza-fluorene-6-carbaldehyde (660 mg, 3 mmol) was added 1.03 gram of magnesium bromide etherate. The mixture was stirred at 23° C. for half an hour. Then a 30 ml dry THF solution of the 6-Bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (1.15 g, 3 mmol) was injected within a minute and the reaction mixture was then cooled to −20° C. Triethylamine (0.7 ml, eq.) was then injected and the reaction mixture was stirred for five hours at −20° C. Then acetic anhydride (0.377 ml, eq.) was injected and the reaction mixture was left at zero degree for 18 hours. The reaction media was then diluted with 400 ml ethyl acetate and washed with 100 ml 5% citric acid, 100 ml saturated sodium bicarbonate, and 100 ml brine. The organic layer was then dried over magnesium sulfate, filtered and concentrated. Flash column chromatography using 20% ethyl acetate in hexane gave 690 mg product. (36% Yield); MS: 644.9 (M+H)

Workup

  1. temperaturethe reaction mixture was then cooled to −20° C
  2. stirringthe reaction mixture was stirred for five hours at −20° C
  3. customThe reaction media
  4. washwashed with 100 ml 5% citric acid, 100 ml saturated sodium bicarbonate, and 100 ml brine
  5. dry with materialThe organic layer was then dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9546579dd0c44c7686d202cfcab474c1
Source dataset
uspto-grants-2006_03
Patent number
US07018997B2

Reaction notes

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