Pyridine → benzhydryl (6R,7R)-8-oxo-3-[(5-oxo-2H-furan-4-yl)methylsulfanyl]-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 467374Notes

Reaction equation

HRID 467374 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=[N:30][O:31][C:32]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]([O-])=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na+].CS(Cl)(=O)=O.N1C=CC=CC=1.[NH2:63][C@@H:64]1[C:95](=[O:96])[N:66]2[C:67]([C:79]([O:81][CH:82]([C:89]3[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=3)[C:83]3[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=3)=[O:80])=[C:68]([S:71][CH2:72][C:73]3[C:74](=[O:78])[O:75][CH2:76][CH:77]=3)[CH2:69][S:70][C@H:65]12>CN(C)C=O>[O:78]=[C:74]1[C:73]([CH2:72][S:71][C:68]2[CH2:69][S:70][C@@H:65]3[C@H:64]([NH:63][C:27](=[O:28])/[C:26](/[C:24]4[N:25]=[C:21]([NH:20][C:1]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=5)([C:8]5[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=5)[C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)[S:22][CH:23]=4)=[N:30]\[O:31][C:32]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[C:95](=[O:96])[N:66]3[C:67]=2[C:79]([O:81][CH:82]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)[C:89]2[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=2)=[O:80])=[CH:77][CH2:76][O:75]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 67908447Diphenylmethyl 7beta-Amino-3-(2,5-dihydro-2-oxofuran-3-ylmethylthio)ceph-3-em-4-carboxylateHCID 74089237Sodium 2-(2-tritylaminothiazol-4-yl)-2-trityloxyiminoacetate

Product 1

HCID 141558983benzhydryl (6R,7R)-8-oxo-3-[(5-oxo-2H-furan-4-yl)methylsulfanyl]-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-50 °C

Procedure

A stirred solution of sodium 2-(2-tritylaminothiazol-4-yl)-2-trityloxyiminoacetate (420 mg) in dimethylformamide (5 ml) was cooled to -50° C. whilst under an inert atmosphere. Methanesulphonyl chloride (0.047 ml) was added and the reaction stirred at -50° C. for 30 min. Pyridine (0.049 ml) was added followed by a solution of diphenylmethyl 7β-amino-3-(2,5-dihydro-2-oxofuran-3-ylmethylthio)ceph-3-em-4-carboxylate (300 mg) in dimethylformamide (3 ml) and the reaction was allowed to warm to 0° C. After stirring at 0° C. for 90 min the mixture was partitioned between ethyl acetate and water. The organic phase was separated and washed twice with water followed by saturated sodium bicarbonate and finally brine. After drying over magnesium sulphate and evaporation of solvent the residue was purified by chromatography on silica gel (Keiselgel, 2:3 ethyl acetate:hexane rising to 7:3 ethyl acetate:hexane). The title compound was isolated as a foam (422 mg). υmax (CH2Cl2) 3380, 1785, 1760 and 1725cm-1 ; δ H (CDCl3) 3.25 (1H, d, J 17.3Hz), 3.49-3.56 (3H, m), 4.68 (2H, s), 5.08 (1H, d, J 4.9Hz), 6.00 (1H, dd, J 8.8Hz, 4.9Hz), 6.44 (1H, s), 6.74 (1H, bs), 6.98 (1H, s), 7.12 (1H, s), 7.16-7.49 (41H, m). [mass spectrum: +ve ion (3NOBA, Na+) MNa+ 1170].

Workup

  1. temperatureto warm to 0° C
  2. stirringAfter stirring at 0° C. for 90 min the mixture
  3. customwas partitioned between ethyl acetate and water
  4. customThe organic phase was separated
  5. washwashed twice with water
  6. dry with materialAfter drying over magnesium sulphate and evaporation of solvent the residue
  7. customwas purified by chromatography on silica gel (Keiselgel, 2:3 ethyl acetate:hexane rising to 7:3 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-14b331df3ec44aef860d33ec5f7ee996
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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