Hydrochloric Acid → 3-[(E)-1-cyclopropylmethyl-2-oxo-pyrrolidin-3-ylidenemethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 581231Notes

Reaction equation

HRID 581231 reaction equation
N[C@@H:2]1[C:9](=[O:10])[N:8]2[C@@H:3]1[S:4][CH2:5][C:6](/[CH:14]=[C:15]1/[C:16](=[O:24])[N:17]([CH2:20][CH:21]3[CH2:23][CH2:22]3)[CH2:18][CH2:19]/1)=[C:7]2[C:11]([OH:13])=[O:12].C(N(CC)CC)C.O.Cl>CN(C)C=O>[CH:21]1([CH2:20][N:17]2[CH2:18][CH2:19]/[C:15](=[CH:14]\[C:6]3[CH2:5][S:4][CH:3]4[N:8]([C:9](=[O:10])[CH2:2]4)[C:7]=3[C:11]([OH:13])=[O:12])/[C:16]2=[O:24])[CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8471TriethylamineHCID 10689147(E)-(6R,7R)-7-Amino-3-(1-cyclopropylmethyl-2-oxo-pyrrolidin-3-ylidenemethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Product 1

HCID 867539163-[(E)-1-cyclopropylmethyl-2-oxo-pyrrolidin-3-ylidenemethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Under an argon atmosphere to a stirred suspension of 25.6 g (E)-(6R,7R)-7-Amino-3-(1-cyclopropylmethyl-2-oxo-pyrrolidin-3-ylidenemethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (73.3 mmol) in 120 ml dimethylformamide was added 20 ml triethylamine (143 mmol) at 10° C. After 15 min, the solution was cooled to 0° C. and 28.5 g (Z)-(2-aminothiazol-4-yl)-acetoxyiminoacetic acid diethoxy thiophosphonyl ester (74.8 mmol) was added in portions over 5 min. Stirring was continued at 0° C. with exclusion of light for 5 h. The reaction was followed by HPLC. The brown reaction mixture was poured at once into 550 ml water of 10° C. Over 30 min, 50 ml HCl 1N was added. The pH dropped from 4.6 to 3.2 and the product precipitated from the reaction mixture. Stirring was continued for 1 h at 0° C. The suspension was filtered. The product was washed with ice-cold water, re-suspended in water, stirred for 20 min at room temperature, filtered and again washed with water. (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-acetoxyimino-acetylamino)]-3-[(E)-1-cyclopropylmethyl-2-oxo-pyrrolidin-3-ylidenemethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid was obtained as a beige, wet solid. The product was used immediately and without drying for the next step.

Workup

  1. waitwas continued at 0° C. with exclusion of light for 5 h
  2. waitOver 30 min
  3. additionThe pH dropped from 4.6 to 3.2
  4. customthe product precipitated from the reaction mixture
  5. stirringStirring
  6. waitwas continued for 1 h at 0° C
  7. filtrationThe suspension was filtered
  8. washThe product was washed with ice-cold water
  9. stirringstirred for 20 min at room temperature
  10. filtrationfiltered
  11. washagain washed with water

Sources & evidence

ORD record
ord-75108b4221744dc685bd11d9cc7076f6
Source dataset
uspto-grants-1999_07
Patent number
US05919939

Reaction notes

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