Triethylamine → HCID 20402464, compound

HRID 1980417Notes

Reaction equation

HRID 1980417 reaction equation
[CH:1]([O:14][C:15]([C:17]1[N:18]2[CH:21]([S:22][CH2:23][C:24]=1[CH:25](Br)[CH:26]=O)[CH:20]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:19]2=[O:37])=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]([NH2:46])(=[S:45])[C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1.CS(Cl)(=O)=O.C(N(CC)CC)C>O1CCCC1.CN(C)C(=O)C.C(OCC)(=O)C>[CH:1]([O:14][C:15]([C:17]1[N:18]2[CH:21]([S:22][CH2:23][C:24]=1[C:25]1[S:45][C:38]([C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)=[N:46][CH:26]=1)[CH:20]([NH:29][C:30]([O:32][C:33]([CH3:35])([CH3:36])[CH3:34])=[O:31])[C:19]2=[O:37])=[O:16])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 27237884-PyridinecarbothioamideHCID 13175928HCID 13175928, compound

Product 1

HCID 20402464HCID 20402464, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of 2-benzhydryloxycarbonyl-3-(1-bromo-2-oxoethyl)-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (mixture of the diastereoisomers) (94 g) in tetrahydrofuran (250 cc) is added in the course of 1 hour 40 minutes to a solution, at 40° C., of thioisonicotinamide (44 g) in N,N-dimethylacetamide (330 cc). The reaction mixture is stirred for 90 minutes at 40°-45° C. and then cooled to -15° C. and treated with methanesulphonyl chloride (18.5 cc) and then triethylamine (53 cc). The mixture is stirred for 1 hour at about -10° C. and then for 16 hours at 25° C. and then diluted with ethyl acetate (1.5 liters) and distilled water (1 liter). The organic phase is washed successively with 0.2 N hydrochloric acid (1.2 liters) and water (2×1 liter), then with a mixture of water (500 cc) and a saturated solution of sodium bicarbonate (150 cc) and finally with water (2×1 liter) and a saturated solution of sodium chloride (200 cc). The residue obtained after evaporation of the solvent to dryness under reduced pressure (30 mm Hg, 4 kPa) at 40° C. is chromatographed on a column (height =56 cm, diameter =80 cm) containing silica gel (0.2-0.06 mm), elution being carried out with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and 800 cc fractions being collected. Fractions 8 to 12 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-3-[2-(pyridin-4-yl)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene (24 g) in the form of a hard brown foam.

Workup

  1. stirringThe mixture is stirred for 1 hour at about -10° C.
  2. waitfor 16 hours at 25° C.
  3. distillationdistilled water (1 liter)
  4. washThe organic phase is washed successively with 0.2 N hydrochloric acid (1.2 liters) and water (2×1 liter)
  5. additionwith a mixture of water (500 cc)
  6. customThe residue obtained
  7. customafter evaporation of the solvent to dryness under reduced pressure (30 mm Hg, 4 kPa) at 40° C.
  8. customis chromatographed on a column (height =56 cm, diameter =80 cm)
  9. additioncontaining
  10. washsilica gel (0.2-0.06 mm), elution
  11. additionbeing carried out with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and 800 cc fractions
  12. custombeing collected
  13. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C.

Sources & evidence

ORD record
ord-e99613db0e9a48e08b6480704169c769
Source dataset
uspto-grants-1985_04
Patent number
US04508717

Reaction notes

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