Dicyclohexylcarbodiimide → HCID 53709484, compound

HRID 1980425Notes

Reaction equation

HRID 1980425 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[NH2:16][CH:17]1[C:24](=[O:25])[N:23]2[CH:18]1[S:19](=[O:56])[CH2:20][C:21]([C:42]1[S:46][C:45]([NH:47][C:48](=[O:55])[C:49]3[CH:54]=[CH:53][CH:52]=[N:51][CH:50]=3)=[N:44][CH:43]=1)=[C:22]2[C:26]([O:28][CH:29]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27].[CH3:57][O:58][N:59]=[C:60]([C:64]1[N:65]=[C:66]([NH:69][C:70]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)([C:77]2[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=2)[C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)[S:67][CH:68]=1)[C:61](O)=[O:62].ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH:29]([O:28][C:26]([C:22]1[N:23]2[CH:18]([S:19](=[O:56])[CH2:20][C:21]=1[C:42]1[S:46][C:45]([NH:47][C:48](=[O:55])[C:49]3[CH:54]=[CH:53][CH:52]=[N:51][CH:50]=3)=[N:44][CH:43]=1)[CH:17]([NH:16][C:61](=[O:62])[C:60](=[N:59][O:58][CH3:57])[C:64]1[N:65]=[C:66]([NH:69][C:70]([C:77]3[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=3)([C:83]3[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=3)[C:71]3[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=3)[S:67][CH:68]=1)[C:24]2=[O:25])=[O:27])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acidHCID 20402453HCID 20402453, compound

Product 1

HCID 53709484HCID 53709484, compoundYield 128.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N'-Dicyclohexylcarbodiimide (1.24 g) is added to a solution, cooled to +5° C., of 7-amino-2-benzhydry-loxycarbonyl-8-oxo-3-(2-nicotinoylaminothiazol-5-yl)-5-thia- 1-azabicyclo[4.2.0]oct-2-ene 5-oxide (2.8g), the syn isomer of 2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid (2.66 g) and 1-hydroxybenzotriazole (0.82 g) in N,N-dimethylformamide (20 cc), and the reaction mixture is then stirred for 1 hour at +5° C. and then for 64 hours at 20° C; after filtration, the reaction mixture is diluted with chloroform (200 cc) and washed with a 5% strength solution of sodium bicarbonate (100 cc), water (100 cc) and then a saturated solution of sodium chloride (100 cc). After drying over magnesium sulphate, the organic phase is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give the crude product (5 g). This crude product (10 g) is chromatographed on a column containing silica gel (0.2-0.06 mm) (250 cc), elution being carried out successively with a mixture of methylene chloride and ethyl acetate (75/25 by volume) (1 liter), then a mixture of methylene chloride and ethyl acetate (50/50 by volume) (1 liter) and then ethyl acetate (2 liters) and a mixture of ethyl acetate and methanol (80/20 by volume) (1 liter) and 100 cc fractions being collected. Fractions 19 to 33 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-nicotinoylaminothiazol-5-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene 5-oxide (6.2 g) in the form of an orange solid.

Workup

  1. filtrationafter filtration
  2. additionthe reaction mixture is diluted with chloroform (200 cc)
  3. washwashed with a 5% strength solution of sodium bicarbonate (100 cc), water (100 cc)
  4. dry with materialAfter drying over magnesium sulphate
  5. concentrationthe organic phase is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C.
  6. customto give the crude product (5 g)
  7. customThis crude product (10 g) is chromatographed on a column
  8. additioncontaining
  9. washsilica gel (0.2-0.06 mm) (250 cc), elution
  10. additionbeing carried out successively with a mixture of methylene chloride and ethyl acetate (75/25 by volume) (1 liter)
  11. additiona mixture of methylene chloride and ethyl acetate (50/50 by volume) (1 liter)
  12. additionethyl acetate (2 liters) and a mixture of ethyl acetate and methanol (80/20 by volume) (1 liter) and 100 cc fractions
  13. custombeing collected
  14. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C.

Sources & evidence

ORD record
ord-a11277e9c97e47959e00d1d15813ed05
Source dataset
uspto-grants-1985_04
Patent number
US04508717

Reaction notes

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