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)methoxy]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 467383Notes

Reaction equation

HRID 467383 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]([O:56][CH2:57][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.O.C(OCC)(=O)C.N1C=CC=CC=1>[O:63]=[C:60]1[CH:59]=[C:58]([CH2:57][O: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

9

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 95660662-(Tritylamino)-alpha-(methoxyimino)-4-thiazoleacetic acid, predominantly syn hydrochlorideHCID 67908486Diphenylmethyl 7beta-Amino-3-(2,5-dihydro-2-oxofuran-4-ylmethyloxy)ceph-3-em-4-carboxylate

Product 1

HCID 88501966benzhydryl (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)methoxy]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-50 °C

Procedure

A stirred solution of 2-(2-tritylaminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid hydrochloride (300 mg) in dimethylformamide (4 ml) was cooled to -50° C. whilst under an inert atmosphere. N,N-Diisopropylethylamine (218 μl) was added followed by methanesulphonyl chloride (49 μl). The reaction was stirred for 30 min. at -50° C. before treating with pyridine (52 μl) followed by a solution of diphenylmethyl 7β-amino-3-(2,5-dihydro-2-oxofuran-4-ylmethyloxy)ceph-3-em-4-carboxylate (300 mg) in dimethylformamide (4 ml) and the temperature allowed to rise to 0° C. The reaction was stirred for 15 min. and then poured into ethyl acetate and water. The organic phase was washed with water (two times) and brine before drying over anhydrous magnesium sulphate. Chromatography on silica gel (Keiselgel) eluting with 4:1 ethyl acetate/hexane gave the title compound which was finally isolated as a foam (431 mg). υmax (CH2Cl2) 3400, 1785, 1755, and 1730cm-1 ; δH(CDCl3) 3.34 (2H, s), 4.08 (3H, s), 4.64 (2H, s) 4.73 (2H, bs), 5.11 (1H, d, J 4.5Hz), 5.79 (1H, dd, J 8.24Hz, 4.5Hz), 5.95 (1H, bs) 6.77 (1H, s), 6.90 (1H, s), 6.96 (1H, d, J 8.07Hz), 7.02 (1H, s), and 7.26-7.39 (25H, m). [Mass spectrum: FAB +ve ion (3NOBA/Na+)MH+ 904, MNa+ 926].

Workup

  1. customto rise to 0° C
  2. stirringThe reaction was stirred for 15 min.
  3. washThe organic phase was washed with water (two times) and brine
  4. dry with materialbefore drying over anhydrous magnesium sulphate
  5. washChromatography on silica gel (Keiselgel) eluting with 4:1 ethyl acetate/hexane

Sources & evidence

ORD record
ord-3a9efdcfefb54507879f5231df179342
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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