Methanesulfonyl chloride → benzhydryl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 467369Notes

Reaction equation

HRID 467369 reaction equation
Cl.[C:2]([NH:21][C:22]1[S:23][CH:24]=[C:25](/[C:27](=[N:31]/[O:32][CH3:33])/[C:28](O)=[O:29])[N:26]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.[NH2:48][C@@H:49]1[C:80](=[O:81])[N:51]2[C:52]([C:64]([O:66][CH:67]([C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)[C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)=[O:65])=[C:53]([CH2:56][S:57][C:58]3[CH2:62][O:61][C:60](=[O:63])[CH:59]=3)[CH2:54][S:55][C@H:50]12>CN(C)C=O.N1C=CC=CC=1>[O:63]=[C:60]1[CH:59]=[C:58]([S:57][CH2:56][C:53]2[CH2:54][S:55][C@@H:50]3[C@H:49]([NH:48][C:28](=[O:29])/[C:27](/[C:25]4[N:26]=[C:22]([NH:21][C:2]([C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=5)([C:3]5[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=5)[C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=5)[S:23][CH:24]=4)=[N:31]\[O:32][CH3:33])[C:80](=[O:81])[N:51]3[C:52]=2[C:64]([O:66][CH:67]([C:74]2[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=2)[C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)=[O:65])[CH2:62][O:61]1

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 95660662-(Tritylamino)-alpha-(methoxyimino)-4-thiazoleacetic acid, predominantly syn hydrochlorideHCID 67908483Diphenylmethyl 7beta-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate

Product 1

HCID 88501491benzhydryl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-3-yl)sulfanylmethyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 76.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent2×

Procedure

A stirred solution of 2-(2-tritylaminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid hydrochloride (528 mg) and N,N-diisopropylethylamine (0.383 ml) in dry dimethylformamide (4 ml) was cooled to -55° to -60° C. and methanesulphonyl chloride (0.085 ml) was added. The mixture was stirred at the same temperature for 30 mins, and then diphenylmethyl 7β-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate (494 mg), dimethylformamide (2 ml) and pyridine (0.08 ml) were added. The mixture was then stirred at 0° for 90 mins. The mixture was partitioned between ethyl acetate and citric acid solution, and the ethyl acetate phase was washed twice with water, then with saturated sodium bicarbonate solution, then water and finally with brine. The solution was dried over magnesium sulphate and evaporated. The title compound (703 mg) was isolated by column chromatography of the residue using gradient elution (Kieselgel 5:2 going to 3:7 hexane:ethyl acetate). υmax (CHCl3), 3400, 1785, 1745, and 1685cm-1. δH (CDCl3) 3.42 (1H, d, J 18.3Hz), 3.61 (1H, d, J 18.4Hz), 3.89 (1H, d, J 12.6Hz), 4.04 (1H, d, J 12.6Hz), 4.08 (3H, s), 4.71 (2H, s), 5.08 (1H, d, J 5.0Hz), 5.65 (1H, s), 5.97 (1H, dd, J 4.9 and 8.8Hz), 6.73 (1H, s), 6.84 (1H, d, J 8.7Hz), 6.96 (1H, s), 7.03 (1H, s), 7.2-7.45 (25H, m). [mass spectrum: +ve ion (3 NOBA, Na+) M Na+ 942].

Workup

  1. stirringThe mixture was then stirred at 0° for 90 mins
  2. customThe mixture was partitioned between ethyl acetate and citric acid solution
  3. washthe ethyl acetate phase was washed twice with water
  4. dry with materialThe solution was dried over magnesium sulphate
  5. customevaporated

Sources & evidence

ORD record
ord-de355ad86c5a413e983ae2e6d8a7f749
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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