Triethylamine → CEPHALOTHIN ANALOG (3-CH3)

HRID 1833893Notes

Reaction equation

HRID 1833893 reaction equation
[NH2:1][C@@H:2]1[C:13](=[O:14])[N:4]2[C:5]([C:10]([OH:12])=[O:11])=[C:6]([CH3:9])[CH2:7][S:8][C@H:3]12.C(N(CC)CC)C.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[CH2:27][C:28](Cl)=[O:29]>C(Cl)Cl>[CH3:9][C:6]1[CH2:7][S:8][C@@H:3]2[C@H:2]([NH:1][C:28](=[O:29])[CH2:27][C:23]3[S:22][CH:26]=[CH:25][CH:24]=3)[C:13](=[O:14])[N:4]2[C:5]=1[C:10]([OH:12])=[O:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 334987-Aminodeacetoxycephalosporanic acidHCID 1623622-Thiopheneacetyl chloride

Product 1

HCID 94457CEPHALOTHIN ANALOG (3-CH3)Yield 68.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of the polymer ester of (6R,7R)-7-amino-3-methylceph-3-em-4-carboxylic acid (5.00g, 5.0 m.mole, from example 18) in methylene chloride (100 ml) was stirred at room temperature (18°-21° ) under nitrogen for 30 minutes. After cooling to 0°, triethylamine (3.03g. 0.03 mole) was added, and stirring continued for 30 minutes. Thienylacetyl chloride (3.0 ml, 3.89g, 0.024 mole) was then added dropwise over a period of 10 minutes maintaining the temperature at 0°-5°. When addition was completed stirring was continued for 15 minutes at 0°-5° and for a further 5 hours at room temperature (18°-21° ). The reaction mixture was filtered and pulled as dry as possible. The product was washed with methylene chloride (3 × 100 ml) acetone (2 × 100 ml), water (4 × 100 ml), acetone (2 × 100 ml), and methylene chloride 3 × 100 ml): and dried to constant weight in vacuo at 40° to give a light brown coloured polymer ester of (6R,7R)-3-methyl-7-(2-thienyl) acetamidoceph-3-em-4-carboxylic acid (5.41g). The composition was confirmed by microanalytical data. ν max (Nujol) 3320w (NH), 1780s (β-lactam CO), 1722s (ester CO) abnd 1688s (amide CO) cm-1, τ [CDCl3 and CF3COOH (2:1)] 2.66 (triplet, J = 3.3 Hz: 2-thienyl proton), 2.97 (doublet, J = 3.3 Hz: 3-thienyl protons): 4.27 (double doublet, J 4.5, 9.0 Hz; 7-H), 4.88 (doublet J 4.5 Hz: 6-H), 5.99 (singlet: --CH2CO--), 6.41 and 6.77 (2 doublets, J 18 - 19 Hz: s-CH2), and 7.70 (singlet, --CH3).

Workup

  1. temperatureAfter cooling to 0°
  2. stirringstirring
  3. waitcontinued for 30 minutes
  4. temperaturemaintaining the temperature at 0°-5°
  5. additionWhen addition
  6. stirringwas completed stirring
  7. waitwas continued for 15 minutes at 0°-5° and for a further 5 hours at room temperature
  8. custom(18°-21° )
  9. filtrationThe reaction mixture was filtered
  10. customas dry as possible
  11. washThe product was washed with methylene chloride (3 × 100 ml) acetone (2 × 100 ml), water (4 × 100 ml), acetone (2 × 100 ml), and methylene chloride 3 × 100 ml): and
  12. customdried to constant weight in vacuo at 40°

Sources & evidence

ORD record
ord-c400e07a7247415491b7bbc3e6ca8376
Source dataset
uspto-grants-1978_01
Patent number
US04067858

Reaction notes

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