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

HRID 376606Notes

Reaction equation

HRID 376606 reaction equation
Cl.[CH3:2][O:3]/[N:4]=[C:5](/[C:9]1[N:10]=[C:11]([NH:14][C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:12][CH:13]=1)\[C:6]([OH:8])=O.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.[NH2:48][C@@H:49]1[C:77](=[O:78])[N:51]2[C:52]([C:65]([O:67][CH2:68][C:69]3[CH:74]=[CH:73][C:72]([O:75][CH3:76])=[CH:71][CH:70]=3)=[O:66])=[C:53]([C@H:56]3[C:60](=C=O)[CH2:59][C@@H:58](OC)[O:57]3)[CH2:54][S:55][C@H:50]12>CN(C)C=O.N1C=CC=CC=1>[CH3:68][O:67][C:65]([C@H:58]1[O:57][C@@H:56]([C:53]2[CH2:54][S:55][C@@H:50]3[C@H:49]([NH:48][C:6](=[O:8])/[C:5](=[N:4]\[O:3][CH3:2])/[C:9]4[N:10]=[C:11]([NH:14][C:15]([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=5)[S:12][CH:13]=4)[C:77](=[O:78])[N:51]3[C:52]=2[C:65]([O:67][CH2:68][C:69]2[CH:70]=[CH:71][C:72]([O:75][CH3:76])=[CH:73][CH:74]=2)=[O:66])[CH2:60][CH2:59]1)=[O:66]

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 95660662-(Tritylamino)-alpha-(methoxyimino)-4-thiazoleacetic acid, predominantly syn hydrochlorideHCID 1317216344-methoxybenzyl (6R,7R)-7-amino-3-[(2R,5S)-5-methoxy-carbonyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

Product 1

HCID 172930338(4-methoxyphenyl)methyl (6R,7R)-3-[(2R,5S)-5-methoxycarbonyloxolan-2-yl]-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 81.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent2×

Procedure

A stirred solution of 2-(Z)methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid hydrochloride (148mg) and N,N-diisopropylethylamine (0.107ml) in dimethylformamide (1ml) was cooled to -55 to -60° C. and methanesulphonyl chloride (0.024ml) was added. The mixture was stirred at the same temperature for 0.5h and then a solution of 4-methoxybenzyl (6R,7R)-7-amino-3-[(2R,5S)-5-methoxy-carbonyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (126mg) in dimethylformamide (1ml) was added followed by pyridine (0.023ml). The mixture was then stirred at 0° C. for 1h and then at room temperature for 0.5h. The mixture was partitioned between ethyl acetate and aqueous citric acid solution, and the organic phase was washed with water, then brine, dried over magnesium sulphate and evaporated. The title compound (100mg) was isolated by column chromatography of the residue (silica gel, 3:7 hexane:ethyl acetate as eluent); vmax (CHCl3) 3403, 1786, 1732 and 1681cm-1 ; δH (CDCl3) 1.66-2.36 (4H, m), 3.58 (1H, d, J 18.0Hz), 3.73 (3H, s), 3.81 (3H, s), 4.02 (1H, d, J 18.0Hz), 4.08 (3H, s), 4.53 (1H, dd, J 3.34, 8.91Hz), 5.02 (1H, d, J 4.8Hz), 5.18 (1H, d, J 11.8Hz), 5.24 (1H, d, J 12.0Hz), 5.30 (1H, dd, J 5.7, 9.9Hz), 5.86 (1H, dd, J 4.6, 8.6Hz), 6.72-6.83 (2H, m), 6.89 (2H, d, J 8.54Hz), 7.01 (1H, s) and 7.25-7.4 (17H, m).

Workup

  1. customThe mixture was partitioned between ethyl acetate and aqueous citric acid solution
  2. washthe organic phase was washed with water
  3. dry with materialbrine, dried over magnesium sulphate
  4. customevaporated

Sources & evidence

ORD record
ord-3306e3034304478b91b7a18db529b2fb
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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