Morpholine → Diphenylmethyl alpha-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(2-bromo-1-morpholinoethylidene)acetate

HRID 971525Notes

Reaction equation

HRID 971525 reaction equation
CS(Cl)(=O)=O.C(C1SC2C(C(=O)N2C(=C(OS(C)(=O)=O)C)C(OC(C2C=CC=CC=2)C2C=CC=CC=2)=O)N=1)C1C=CC=CC=1.N1CCOCC1.[CH2:51]([C:58]1[S:64][CH:63]2[CH:60]([C:61](=[O:90])[N:62]2[C:65](=[C:82]([N:84]2[CH2:89][CH2:88][O:87][CH2:86][CH2:85]2)[CH3:83])[C:66]([O:68][CH:69]([C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)[C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)=[O:67])[N:59]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.[Br:91]Br>O1CCCC1.N1C=CC=CC=1.C(N(CC)CC)C>[CH2:51]([C:58]1[S:64][CH:63]2[CH:60]([C:61](=[O:90])[N:62]2[C:65](=[C:82]([N:84]2[CH2:85][CH2:86][O:87][CH2:88][CH2:89]2)[CH2:83][Br:91])[C:66]([O:68][CH:69]([C:76]2[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=2)[C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)=[O:67])[N:59]=1)[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1

Participants

9

Reactant 5

HCID 8083MorpholineHCID 24408BromineHCID 31297Methanesulfonyl chlorideHCID 70504342Diphenylmethyl α-[1-(4-morpholinyl)ethylidene]-7-oxo-3-(phenylmethyl)-4-thia-2,6-diazabicyclo[3.2.0]hept-2-ene-6-acetateHCID 88716344Diphenylmethyl alpha-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(1-methanesulfonyloxyethylidene)acetate

Product 1

HCID 54517846Diphenylmethyl alpha-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(2-bromo-1-morpholinoethylidene)acetateYield 70%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

One dissolves diphenylmethyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-hdyroxyethylidene)acetate (4.84 g) in tetrahydrofuran (60 ml), cools to -20° C., adds triethylamine (2.84 ml) with stirring, adds dropwise methanesulfonyl chloride (0.82 ml) to the yellow solution, and lets react for 30 minutes. To the produced solution of diphenylmethyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-methanesulfonyloxyethylidene)acetate, one adds morpholine (0.96 ml) at -40° C., stirrs for 3.5 hours, adds pyridine (0.77 ml) to the produced solution of diphenylmethyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-morpholinoethylidene)acetate, cools to -40° C., adds bromine (0.49 ml), and stirs for 30 minutes to give diphenylmethyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α -(2-bromo-1-morpholinoethylidene)acetate. To this solution, one adds dropwise for 3 hours at room temperature 5% hydrochloric acid (72 ml) and methanol (60 ml), stirs, and keeps in a refrigerator overnight. The reaction mixture is evaporated to give residue which is dissolved in methylene chloride, washed with water, dried over sodium sulfate, and evaporated. Purification of the obtained residue (5.83 g) by chromatography over silica gel containing 10% water (150 g) gives from the fraction eluted with a mixture of benzene and ethyl acetate (4:1) diphenylmethyl 7-phenylacetamido-3hyroxy-3-cephem-4-carboxylate (3.51 g) by recrystallization from n-hexane. m.p. 93°-96° C. Yield: 70%. IR: νmaxCHCl3 3410, 1782, 1674, 1610 cm-1. NMR: δCDCl3 3.20s2H, 3.64s2H, 4.97d(4Hz)1H, 5.66dd(9:4Hz)1H, 6.77d (9Hz)1H, 6.90s1H, 7.35m15H.

Workup

  1. customcools to -20° C.
  2. customlets react for 30 minutes
  3. customcools to -40° C.

Sources & evidence

ORD record
ord-83e16a7fe8e9436d98d99ee4846ca81b
Source dataset
uspto-grants-1979_07
Patent number
US04160085

Reaction notes

Loading…