Dicyclohexylcarbodiimide → HCID 68136555, compound

HRID 258703Notes

Reaction equation

HRID 258703 reaction equation
[CH3:1][S:2][C:3]1[N:4]([CH2:8][C:9]([OH:11])=O)[CH:5]=[CH:6][N:7]=1.[C:12]([O:15][CH2:16][C:17]1[CH2:24][S:23][CH:22]2[N:19]([C:20](=[O:26])[CH:21]2[NH2:25])[C:18]=1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])(=[O:14])[CH3:13].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[C:12]([O:15][CH2:16][C:17]1[CH2:24][S:23][CH:22]2[N:19]([C:20](=[O:26])[CH:21]2[NH:25][C:9](=[O:11])[CH2:8][N:4]2[CH:5]=[CH:6][N:7]=[C:3]2[S:2][CH3:1])[C:18]=1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])(=[O:14])[CH3:13]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 11771800HCID 11771800, compoundHCID 21426445HCID 21426445, compound

Product 1

HCID 68136555HCID 68136555, compoundYield 42.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

(2-methylthio-imidazol-1-yl)-acetic acid (10.3 g.) is dissolved in dimethylformamide (360 cc.), by heating to 50° C. After cooling, 3-acetoxymethyl-7-amino-2-(tertiary butoxycarbonyl)-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene (21.4 g.) and dicyclohexylcarbodiimide (13.5 g.) are added. The reagents are contacted for 18 hours, with stirring, at a temperature of about 20° C., and then the solid is filtered off. The filtrate is taken up in ethyl acetate (2.5 liters) and is washed with a saturated aqueous solution of sodium bicarbonate and then with water. Extraction is then effected using N hydrochloric acid (400 cc.), and the acid aqueous phase is washed with ethyl ether and then brought to pH 8 by adding a 4 N solution of sodium hydroxide. The oil which separates out is extracted with methylene chloride (500 cc.). The methylene chloride extracts are washed with water, dried over sodium sulphate, treated with decolorising charcoal and concentrated to dryness under reduced pressure (20 mm.Hg.). An orange-yellow oily residue (30.2 g.) is obtained and is purified by crystallisation from a mixture of methanol (32 cc.) and isopropyl ether (210 cc.) to give 3-actoxymethyl-2-(tertiary butoxycarbonyl)-7-[(2-methylthio-imidazol-1-yl)-acetamido]-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene (12.3 g.), m.p. 170° C.

Workup

  1. temperatureAfter cooling
  2. filtrationthe solid is filtered off
  3. washis washed with a saturated aqueous solution of sodium bicarbonate
  4. extractionExtraction
  5. washthe acid aqueous phase is washed with ethyl ether
  6. additionby adding a 4 N solution of sodium hydroxide
  7. extractionThe oil which separates out is extracted with methylene chloride (500 cc.)
  8. washThe methylene chloride extracts are washed with water
  9. dry with materialdried over sodium sulphate
  10. additiontreated with decolorising charcoal
  11. concentrationconcentrated to dryness under reduced pressure (20 mm.Hg.)
  12. customAn orange-yellow oily residue (30.2 g.) is obtained
  13. customis purified by crystallisation from a mixture of methanol (32 cc.) and isopropyl ether (210 cc.)

Sources & evidence

ORD record
ord-cadbcb410c2a4aadad4b54b0cc586c81
Source dataset
uspto-grants-1977_07
Patent number
US04034088

Reaction notes

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