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

HRID 376590Notes

Reaction equation

HRID 376590 reaction equation
S(Cl)(C)(=O)=O.[CH3:6][O:7]/[N:8]=[C:9](/[C:13]1[NH:14][N:15]([NH:18][C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[S:16][CH:17]=1)\[C:10]([OH:12])=O.C(N(CC)C(C)C)(C)C.[NH2:47][C@@H:48]1[C:72](=[O:73])[N:50]2[C:51]([C:60]([O:62][CH2:63][C:64]3[CH:69]=[CH:68][C:67]([O:70][CH3:71])=[CH:66][CH:65]=3)=[O:61])=[C:52]([C@@H:55]3[CH2:59][CH2:58][CH2:57][O:56]3)[CH2:53][S:54][C@H:49]12>ClCCl.N1C=CC=CC=1>[CH3:6][O:7]/[N:8]=[C:9](/[C:13]1[NH:14][N:15]([NH:18][C:19]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[S:16][CH:17]=1)\[C:10]([NH:47][C@@H:48]1[C:72](=[O:73])[N:50]2[C:51]([C:60]([O:62][CH2:63][C:64]3[CH:69]=[CH:68][C:67]([O:70][CH3:71])=[CH:66][CH:65]=3)=[O:61])=[C:52]([C@@H:55]3[CH2:59][CH2:58][CH2:57][O:56]3)[CH2:53][S:54][C@H:49]12)=[O:12]

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 18780107(2Z)-2-methoxyimino-2-[2-(tritylamino)-3H-thiadiazol-4-yl]acetic acidHCID 538410264-methoxybenzyl (6R,7R)-7-amino-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

Product 1

HCID 141582264(4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-3H-thiadiazol-4-yl]acetyl]amino]-8-oxo-3-[(2S)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 44.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

Mesyl chloride (65μl) was added to 2-(Z)-methoxyimino-2-(2-tritylaminothiadiazol-4-yl)acetic acid (370mg) and N,N-diisopropylethylamine (146μl) in dichloromethane (5ml) at -20° C. The reaction mixture was stirred at -20° C. for 1 hour then added to an ice cold solution of 4-methoxybenzyl (6R,7R)-7-amino-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (335mg) and pyridine (70μl) in dichloromethane (5ml). The reaction was stirred for 1 hour, concentrated and flash chromatographed on silica gel eluting with 30,50,60 and 70% ethyl acetate in hexane to afford the title compound as a foam (300mg); vmax (CHCl3) 3398, 1784, 1724, 1691, 1516, 1134 and 1107 cm-1 ; δH (CDCl3, 250MHz) 1.55-1.75 (1H,m), 1.80-2.05 (2H,m), 2.25-2.45 (1H,m), 3.30 and 3.61 (2H, ABq, J 18.3Hz), 3.75-4.00 (2H,m), 3.81 (3H,m), 4.16 (3H,m), 4.85-5.00 (1H,m), 5.00 (1H,d, J 4.8Hz), 5.17 (2H,s), 5.92 (1H,dd, J 4.8Hz), 6.72 (1H,d,J 7.8Hz) and 6.88 and 7.30 (19H,m). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (839)].

Workup

  1. stirringThe reaction was stirred for 1 hour
  2. concentrationconcentrated
  3. customflash chromatographed on silica gel eluting with 30,50,60 and 70% ethyl acetate in hexane

Sources & evidence

ORD record
ord-289e345f58254e1fae80e0bf1e12728c
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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