Hydrochloric Acid → 3-Acetonyl-2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 463588Notes

Reaction equation

HRID 463588 reaction equation
C(Cl)(Cl)=O.[CH3:5][O:6][N:7]=[C:8]([C:12]1[N:13]=[C:14]([NH:17][C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[S:15][CH:16]=1)[C:9](O)=[O:10].[CH2:37]([C:41]1[CH2:48][S:47][CH:46]2[N:43]([C:44](=[O:50])[CH:45]2[NH2:49])[C:42]=1[C:51]([O:53][CH:54]([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:52])[C:38]([CH3:40])=[O:39].Cl>C1C=CC=CC=1.C(Cl)Cl.CN(C)C(=O)C.C(N(CC)CC)C>[CH2:37]([C:41]1[CH2:48][S:47][CH:46]2[N:43]([C:44](=[O:50])[CH:45]2[NH:49][C:9](=[O:10])[C:8](=[N:7][O:6][CH3:5])[C:12]2[N:13]=[C:14]([NH:17][C:18]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[S:15][CH:16]=2)[C:42]=1[C:51]([O:53][CH:54]([C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=1)[C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)=[O:52])[C:38]([CH3:40])=[O:39]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 6371PhosgeneHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acidHCID 202811313-Acetonyl-7-amino-2-benzhydryloxycarbonyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Product 1

HCID 544195633-Acetonyl-2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-eneYield 35.8%

Reagents, catalysts & solvents 4

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

A 2.5M solution of phosgene in benzene (6.47 cc) is added, in the course of 20 minutes, to a suspension of 2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid (syn isomer) (5.84 g) in a mixture of methylene chloride (50 cc) and N,N-dimethylacetamide (1.23 cc) at -10° C. The reaction is left to proceed for 16 hours at -10° C. and a solution of 3-acetonyl-7-amino-2-benzhydryloxycarbonyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (5.57 g) in a mixture of methylene chloride (50 cc) and triethylamine (5.6 cc) is then added in the course of 20 minutes. The mixture is stirred for 2 hours at -10° C. 0.5N hydrochloric acid (100 cc) is added and the organic phase is separated off by decantation. It is dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is chromatographed on a column of Merck silica gel (0.06-0.2) (130 g) (diameter of the column: 3 cm; height: 37 cm). Elution is carried out with a 40/60 (by volume) ethyl acetate/cyclohexane mixture (2 liters), 100 cc fractions being collected. Fractions 8 to 14 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. This yields the syn isomer of 3-acetonyl-2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (4 g), which is identical to the product prepared above under A.

Workup

  1. waitThe reaction is left
  2. additionis then added in the course of 20 minutes
  3. customthe organic phase is separated off by decantation
  4. dry with materialIt is dried over sodium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C
  6. customThe residue is chromatographed on a column of Merck silica gel (0.06-0.2) (130 g) (diameter of the column
  7. washElution
  8. custombeing collected
  9. concentrationFractions 8 to 14 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C

Sources & evidence

ORD record
ord-9468054bb3ce47c68e9de1ef72aed621
Source dataset
uspto-grants-1985_05
Patent number
US04520193

Reaction notes

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