Acetic Acid → HCID 54463668, compound

HRID 1980420Notes

Reaction equation

HRID 1980420 reaction equation
[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:9]=[C:10]([NH:13][C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[S:11][CH:12]=1)[C:5](O)=[O:6].ON1C2C=CC=CC=2N=N1.[NH2:43][CH:44]1[C:51](=[O:52])[N:50]2[CH:45]1[S:46][CH2:47][C:48]([C:69]1[S:73][C:72]([CH2:74][C:75]3[CH:76]=[N:77][CH:78]=[CH:79][CH:80]=3)=[N:71][CH:70]=1)=[C:49]2[C:53]([O:55][CH:56]([C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)=[O:54].C(O)(=O)C>CN(C)C=O>[CH:56]([O:55][C:53]([C:49]1[N:50]2[CH:45]([S:46][CH2:47][C:48]=1[C:69]1[S:73][C:72]([CH2:74][C:75]3[CH:76]=[N:77][CH:78]=[CH:79][CH:80]=3)=[N:71][CH:70]=1)[CH:44]([NH:43][C:5](=[O:6])[C:4](=[N:3][O:2][CH3:1])[C:8]1[N:9]=[C:10]([NH:13][C:14]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[S:11][CH:12]=1)[C:51]2=[O:52])=[O:54])([C:63]1[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 757711-HydroxybenzotriazoleHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acidHCID 13960529HCID 13960529, compound

Product 1

HCID 54463668HCID 54463668, compoundYield 56.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

The syn isomer of 2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid (5.32 g), 3-hydroxybenzotriazole (1.62 g) and N,N-dicyclohexylcarbodiimide (2.47 g) are added to a solution, cooled to +5° C., of 7-amino-2-benzhydryloxycarbonyl-8-oxo-3-[2-(pyridin-3-yl-methyl)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene (5.4 g) in N,N-dimethylformamide (100 cc). The mixture is stirred for 1 hour at 5° C., the temperature is then allowed to rise and the mixture is stirred for 4 hours at 23° C. Acetic acid (0.5 cc) is added, the mixture is stirred for 5 minutes and the suspension is filtered. The filtrate is poured into a 50/50 (by volume) mixture of water and ethyl acetate (500 cc). The organic phase is decanted and then washed successively with a 0.1 N solution of hydrochloric acid (100 cc), a saturated solution of sodium bicarbonate (100 cc), distilled water (100 cc) and a saturated solution of sodium chloride (100 cc). It is dried over anhydrous sodium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 30° C. The residue is purified by chromatography on silica gel (0.05-0.2 mm) (height of silica: 77 cm, diameter of the column: 3.5 cm), elution being carried out with a 20/80 (by volume) mixture of cyclohexane and ethyl acetate (1 liter) and then with a 10/90 (by volume) mixture of cyclohexane and ethyl acetate (3.8 liters) and 60 cc fractions being collected. Fractions 39 to 80 are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa). This gives the syn isomer of 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-[2-(pyridin-3-yl-methyl)thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene (5.43 g) in the form of a hard yellow foam.

Workup

  1. stirringthe mixture is stirred for 4 hours at 23° C
  2. stirringthe mixture is stirred for 5 minutes
  3. filtrationthe suspension is filtered
  4. additionThe filtrate is poured into a 50/50 (by volume) mixture of water and ethyl acetate (500 cc)
  5. customThe organic phase is decanted
  6. washwashed successively with a 0.1 N solution of hydrochloric acid (100 cc)
  7. distillationa saturated solution of sodium bicarbonate (100 cc), distilled water (100 cc)
  8. dry with materialIt is dried over anhydrous sodium sulphate
  9. filtrationfiltered
  10. concentrationthe filtrate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 30° C
  11. customThe residue is purified by chromatography on silica gel (0.05-0.2 mm) (height of silica
  12. wash77 cm, diameter of the column: 3.5 cm), elution
  13. additionbeing carried out with a 20/80 (by volume) mixture of cyclohexane and ethyl acetate (1 liter)
  14. additionwith a 10/90 (by volume) mixture of cyclohexane and ethyl acetate (3.8 liters) and 60 cc fractions
  15. custombeing collected
  16. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa)

Sources & evidence

ORD record
ord-212c2ab462d64cc287c7c4c31f453572
Source dataset
uspto-grants-1985_04
Patent number
US04508717

Reaction notes

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