Methanesulfonyl chloride → HCID 20402445, compound

HRID 1980414Notes

Reaction equation

HRID 1980414 reaction equation
[C:1]([NH2:9])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH:10]([O:23][C:24]([C:26]1[N:27]2[CH:30]([S:31][CH2:32][C:33]=1[CH:34](Br)[CH:35]=O)[CH:29]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C:28]2=[O:46])=[O:25])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C.N1C=CC=CC=1>[CH:10]([O:23][C:24]([C:26]1[N:27]2[CH:30]([S:31][CH2:32][C:33]=1[C:34]1[S:8][C:1]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=3)=[N:9][CH:35]=1)[CH:29]([NH:38][C:39]([O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[O:40])[C:28]2=[O:46])=[O:25])([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 737155ThionicotinamideHCID 13175928HCID 13175928, compound

Product 1

HCID 20402445HCID 20402445, compound

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Thionicotinamide (28.2 g) and pyridine (16.5 cc) are added to 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) (120 g) in tetrahydrofuran (1,200 cc). The reaction mixture is stirred at 50° C. for 80 minutes. After cooling to +5° C., methanesulphonyl chloride (15.8 cc) and triethylamine (57.3 cc) are added successively in the course of 5 minutes. The reaction mixture is kept for 30 minutes at +5° C. and then reheated to 20° C. and poured into a mixture of ethyl acetate (1 liter) and a 5% strength solution of sodium bicarbonate (2 liters). The organic phase is washed with a 5% strength solution of sodium bicarbonate (2 liters) and then with a semi-saturated solution of sodium chloride (2 liters). After drying over magnesium sulphate and evaporation of the solvent to dryness under reduced pressure (4 kPa) at 30° C., the residue obtained is chromatographed on a column of diameter 9 cm containing silica gel (0.06-0.2 mm) (3.4 liters), 1 liter. fractions being collected. Elution is carried out successively with: methylene chloride (11 liters) and then the following mixtures (proportions by volume) of methylene chloride and ethyl acetate: 94/6 (16 liters), 88/12 (4 liters), 75/25 (12 liters) and 70/30 (10 liters). Fractions 32 to 52 are combined and concentrated to dryness and the residue is solidified with isopropyl ether to give 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-3-[2-(pyridin-3-yl)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]-oct-2-ene (37.1 g) in the form of a beige solid.

Workup

  1. temperatureAfter cooling to +5° C.
  2. waitThe reaction mixture is kept for 30 minutes at +5° C.
  3. customreheated to 20° C.
  4. washThe organic phase is washed with a 5% strength solution of sodium bicarbonate (2 liters)
  5. dry with materialAfter drying over magnesium sulphate and evaporation of the solvent to dryness under reduced pressure (4 kPa) at 30° C.
  6. customthe residue obtained
  7. customis chromatographed on a column of diameter 9 cm
  8. additioncontaining silica gel (0.06-0.2 mm) (3.4 liters), 1 liter
  9. customfractions being collected
  10. washElution
  11. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-d43a1a632d864076bd84e43e1aa1b79e
Source dataset
uspto-grants-1985_04
Patent number
US04508717

Reaction notes

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