Phosgene → HCID 53770919, compound

HRID 1980413Notes

Reaction equation

HRID 1980413 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].[NH2:37][CH:38]1[C:45](=[O:46])[N:44]2[CH:39]1[S:40](=[O:74])[CH2:41][C:42]([C:63]1[S:67][C:66]([C:68]3[CH:69]=[N:70][CH:71]=[CH:72][CH:73]=3)=[N:65][CH:64]=1)=[C:43]2[C:47]([O:49][CH:50]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:48].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl.CN(C)C(=O)C>[CH:50]([O:49][C:47]([C:43]1[N:44]2[CH:39]([S:40](=[O:74])[CH2:41][C:42]=1[C:63]1[S:67][C:66]([C:68]3[CH:69]=[N:70][CH:71]=[CH:72][CH:73]=3)=[N:65][CH:64]=1)[CH:38]([NH:37][C:9](=[O:10])[C:8](=[N:7][O:6][CH3:5])[C:12]1[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]=1)[C:45]2=[O:46])=[O:48])([C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

8

Reactant 4

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acidHCID 20402451HCID 20402451, compound

Product 1

HCID 53770919HCID 53770919, compoundYield 43.5%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
-10 °C

Procedure

A 2 M solution of phosgene in toluene (32.6 cc) is added dropwise to a solution of the syn form of 2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid (25 g) in a mixture of dry methylene chloride (500 cc) and N,N-dimethylacetamide (5.25 cc), cooled to -10° C. The reaction mixture is stirred for 3 hours 30 minutes at between -5° and 0° C. and N,N-dimethylacetamide (15.8 cc) and a solution of 7-amino-2-benzhydryloxycarbonyl-8-oxo-3-[2-(pyridin-3-yl)-thiazol-5-yl]-5-thia-1-azabicyclo-[4.2.0]oct-2-ene 5-oxide (26 g) in methylene chloride (200 cc) are then added at -5° C. The reaction mixture is stirred for 1 hour 30 minutes at between 0° and +5° C. and then for 16 hours at 20° C. and is then treated with a 5% strength solution of sodium bicarbonate (500 cc) and filtered. The organic phase is washed with a semi-saturated solution of sodium chloride (500 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue is chromatographed on a column (height=52 cm, diameter=7 cm) of silica gel (0.06-0.2 mm), ethyl acetate being used as the eluent and 1 liter fractions being collected. Fractions 6 to 13 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give the syn isomer of 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-[2-(pyridin-3-yl)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2 .0]-oct-2-ene 5-oxide (20.2 g) in the form of a cream solid (by taking up the resulting hard foam in methylene chloride (80 cc) and precipitating the product with isopropyl ether (300 cc)).

Workup

  1. stirringThe reaction mixture is stirred for 1 hour 30 minutes at between 0° and +5° C.
  2. waitfor 16 hours at 20° C.
  3. filtrationfiltered
  4. washThe organic phase is washed with a semi-saturated solution of sodium chloride (500 cc)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  7. customThe residue is chromatographed on a column (height=52 cm, diameter=7 cm) of silica gel (0.06-0.2 mm), ethyl acetate being
  8. custombeing collected
  9. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C.

Sources & evidence

ORD record
ord-cb99ec14237f4146bcd1a64b8272b666
Source dataset
uspto-grants-1985_04
Patent number
US04508717

Reaction notes

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