1,3-Bis(trimethylsilyl)urea → benzhydryl (6R,7R)-7-[[(2Z)-2-acetyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 992707Notes

Reaction equation

HRID 992707 reaction equation
[NH2:1][C@@H:2]1[C:32](=[O:33])[N:4]2[C:5]([C:16]([O:18][CH:19]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])=[C:6]([S:9][CH2:10][C:11]3[CH:12]=[N:13][NH:14][CH:15]=3)[CH2:7][S:8][C@H:3]12.C[Si](C)(C)NC(N[Si](C)(C)C)=O.[NH2:46][C:47]1[S:48][CH:49]=[C:50](/[C:52](=[N:56]/[O:57][C:58](=[O:60])[CH3:59])/[C:53](Cl)=[O:54])[N:51]=1.C(=O)(O)[O-].[Na+]>C1COCC1.C(#N)C.C(OCC)(=O)C>[NH2:46][C:47]1[S:48][CH:49]=[C:50](/[C:52](=[N:56]/[O:57][C:58](=[O:60])[CH3:59])/[C:53]([NH:1][C@@H:2]2[C:32](=[O:33])[N:4]3[C:5]([C:16]([O:18][CH:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:17])=[C:6]([S:9][CH2:10][C:11]4[CH:15]=[N:14][NH:13][CH:12]=4)[CH2:7][S:8][C@H:3]23)=[O:54])[N:51]=1

Participants

8

Reactant 4

HCID 875621,3-Bis(trimethylsilyl)ureaHCID 516892Sodium BicarbonateHCID 11322595[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-chloro-2-oxoethylidene]amino] acetateHCID 70122266Diphenylmethyl 7beta-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate

Product 1

HCID 88158439benzhydryl (6R,7R)-7-[[(2Z)-2-acetyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
35 °C

Procedure

Under nitrogen atmosphere, to a suspension of diphenylmethyl 7β-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (30.2 g) in THF (800 ml) was added herein 1,3-bis(trimethylsilyl)urea (25.8 g) was added at the room temperature. The reaction mixture was warmed at 35° C. and dissolved, and then it was cooled below 0° C. A suspension of 2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetylchloride monohydrochiloride salt (17.93 g) in acetonitrile (200 ml) was dropped into the above reaction mixture below 0° C. After stirring at the same temperature for 10 minutes, it was poured into a mixture of ethyl acetate (1.2 l) and ice-water (1.5 l). The aqueous layer was adjusted at pH 6.5 with saturated sodium bicarbonate solution. The organic layer was separated, washed with brine (1.0 l), and dried over magnesium sulfate, and then evaporated until the volume amounted to 500 ml. The solution was poured into IPE (1.5 l). The resulting precipitate was filtered, dried under reduced pressure to give diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (41.3 g) as powder.

Workup

  1. additionwas added at the room temperature
  2. dissolutiondissolved
  3. temperatureit was cooled below 0° C
  4. additionwas dropped into the above reaction mixture below 0° C
  5. customThe organic layer was separated
  6. washwashed with brine (1.0 l)
  7. dry with materialdried over magnesium sulfate
  8. customevaporated until the volume
  9. additionThe solution was poured into IPE (1.5 l)
  10. filtrationThe resulting precipitate was filtered
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-b7c71077da35489a8f8cb2c4e1afde81
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

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