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-4-yl)methylsulfanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 467373Notes

Reaction equation

HRID 467373 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]([OH:30])=O)[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(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[C:48]1([CH:54]([O:61][C:62]([C:64]2[N:69]3[C:70](=[O:73])[C@@H:71]([NH2:72])[C@H:68]3[S:67][CH2:66][C:65]=2[S:74][CH2:75][C:76]2[C:77](=[O:81])[O:78][CH2:79][CH:80]=2)=[O:63])[C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>CN(C)C=O.C(OCC)(=O)C.O.N1C=CC=CC=1>[O:81]=[C:77]1[C:76]([CH2:75][S:74][C:65]2[CH2:66][S:67][C@@H:68]3[C@H:71]([NH:72][C:28](=[O:30])/[C:27](/[C:25]4[N:26]=[C:22]([NH:21][C:2]([C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=5)([C:3]5[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=5)[C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=5)[S:23][CH:24]=4)=[N:31]\[O:32][CH3:33])[C:70](=[O:73])[N:69]3[C:64]=2[C:62]([O:61][CH:54]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)=[O:63])=[CH:80][CH2:79][O:78]1

Participants

8

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 95660662-(Tritylamino)-alpha-(methoxyimino)-4-thiazoleacetic acid, predominantly syn hydrochlorideHCID 67908447Diphenylmethyl 7beta-Amino-3-(2,5-dihydro-2-oxofuran-3-ylmethylthio)ceph-3-em-4-carboxylate

Product 1

HCID 88501698benzhydryl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-4-yl)methylsulfanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 66.2%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent2×HCID 22728543Water ethylacetateSolvent

Conditions

Temperature
-50 °C

Procedure

A stirred solution of 2-(2-Tritylaminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid hydrochloride (287 mg) and diisopropylethylamine (0.208 ml) in dry dimethylformamide (5 ml) was cooled to -50° C. under an inert atmosphere. Treatment with methanesulfonyl chloride (0.047 ml) was followed by stirring at -50° C. for 45 min. Pyridine (0.048 ml) and a solution of diphenylmethyl-7β-amino-3-(2,5-dihydro-2-oxofuran-3-ylmethylthio)ceph-3-em-4-carboxylate (298 mg) in dimethylformamide (3 ml) were then added and the reaction allowed to warm to 0° C. The reaction was stirred at 0° C. for 90 min. before pouring into ethyl acetate/water. The ethyl acetate was separated and washed three times with water, saturated sodium bicarbonate solution, and brine before drying over magnesium sulphate. Evaporation of solvent and chromatography of the residue on silica gel(Keiselgel 7:3 ethyl acetate:hexane) gave the title compound (364 mg). υmax (CH2Cl2) 3400, 1780, and 1760cm-1 ; δH (CDCl3) 3.50 (1H, d, J 17.4Hz), 3.53 (2H, s), 3.67 (1H, d, J 17.4Hz), 4.08 (3H, s), 4.72 (2H, s), 5.08 (1H, d, J 4.7Hz), 5.88 (1H, dd, J 8.6Hz, 4.7Hz), 6.76 (1H, s), 6.83 (1H, d, J 8.8Hz), 6.90 (1H, s), 6.95 (1H, s), 7.16-7.46 (26H, m). [mass spectrum: +ve ion (3NOBA, Na+) MNa+ 942].

Workup

  1. temperatureto warm to 0° C
  2. stirringThe reaction was stirred at 0° C. for 90 min.
  3. customThe ethyl acetate was separated
  4. washwashed three times with water, saturated sodium bicarbonate solution, and brine
  5. dry with materialbefore drying over magnesium sulphate
  6. customEvaporation of solvent and chromatography of the residue on silica gel(Keiselgel 7:3 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-6d9c2076bc1041c3a6edb2777ce19b3c
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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