Pyridine → tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(2S)-5-oxooxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 6291Notes

Reaction equation

HRID 6291 reaction equation
CS(Cl)(=O)=O.[CH3:6][O:7]/[N:8]=[C:9](/[C:13]1[N:14]=[C: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]([O-:12])=O.[Na+].[NH2:39][C@@H:40]1[C:60](=[O:61])[N:42]2[C:43]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])=[C:44]([C@H:47]3[O:51][C:50](=[O:52])[CH2:49][CH2:48]3)[CH2:45][S:46][C@H:41]12.N1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[CH3:6][O:7]/[N:8]=[C:9](/[C:13]1[N:14]=[C:15]([NH:18][C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([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)[S:16][CH:17]=1)\[C:10]([NH:39][C@@H:40]1[C:60](=[O:61])[N:42]2[C:43]([C:53]([O:55][C:56]([CH3:57])([CH3:58])[CH3:59])=[O:54])=[C:44]([C@H:47]3[O:51][C:50](=[O:52])[CH2:49][CH2:48]3)[CH2:45][S:46][C@H:41]12)=[O:12]

Participants

7

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 23671647sodium (2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetateHCID 57283631t-butyl (6R,7R)-7-amino-3-[(5S)-2-oxotetrahydrofuran-5-yl]ceph-3-em-4-carboxylate

Product 1

HCID 141579557tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-[(2S)-5-oxooxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 60.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

Methanesulphonyl chloride (23 μl, 0.3 mmol) was added to sodium 2-(Z)-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetate (0.12 g,0.25 mmol) in DMF (0.5 ml) at -40° C. The mixture was allowed to warm to -10° C. over 0.5 h then cooled to -30° C. and t-butyl (6R,7R)-7-amino-3-[(5S)-2-oxotetrahydrofuran-5-yl]ceph-3-em-4-carboxylate (68 mg, 0.2 mmol) in DMF (1 ml) and pyridine (24 μl, 0.3 mmol) was added. The reaction was stirred for 1 h without cooling, then diluted with ethyl acetate, washed twice with water and brine, dried, concentrated and flash chromatographed, eluting with 40,50% ethyl acetate in hexane, to give the title compound (92 mg,60%), δH (CDCl3) 1.53 (9H,m), 1.9-2.1 (1H,m), 2.5-2.8 3H,m), 3.27 and 3.57 (2H,ABq,J18.7 Hz), 4.07 (3H,s), 5.06 (1H,d,J5Hz), 5.6-5.8 (1H,m), 5.98 (1H,dd,J5,9 Hz), 6.72 (1H,d,J9 Hz), 6.74 (1H,s), 7.02 (1H,s), 7.2-7.4 (15H,m); [mass spectrum: +ve ion (thioglycerol)MH+, 766].

Workup

  1. temperaturethen cooled to -30° C.
  2. temperaturewithout cooling
  3. washwashed twice with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customflash chromatographed
  7. washeluting with 40,50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-aaa752085c62402d8beb5b3c0698a75a
Source dataset
uspto-grants-1993_09
Patent number
US05246926

Reaction notes

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