Sodium Iodide → 2-Naphthylmethyl 3-methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylate

HRID 2296576Notes

Reaction equation

HRID 2296576 reaction equation
[CH3:1][C:2]1[CH2:3][S:4][C@@H:5]2[CH:12]([NH:13][C:14](=[O:35])[CH:15]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[NH:16][C:17]([N:19]3[CH2:24][CH2:23][N:22]([CH2:25][CH3:26])[C:21](=[O:27])[C:20]3=[O:28])=[O:18])[C:11](=[O:36])[N:6]2[C:7]=1[C:8]([OH:10])=[O:9].C(N(CC)CC)C.C(=O)(O)[O-].[K+].[I-].[Na+].Br[CH2:52][C:53]1[CH:62]=[CH:61][C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:54]=1>C(OCC)(=O)C.O.CC(C)=O.CN(C)C=O>[CH3:1][C:2]1[CH2:3][S:4][C@@H:5]2[CH:12]([NH:13][C:14](=[O:35])[CH:15]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[NH:16][C:17]([N:19]3[CH2:24][CH2:23][N:22]([CH2:25][CH3:26])[C:21](=[O:27])[C:20]3=[O:28])=[O:18])[C:11](=[O:36])[N:6]2[C:7]=1[C:8]([O:10][CH2:52][C:53]1[CH:62]=[CH:61][C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:54]=1)=[O:9]

Participants

10

Reactant 5

HCID 5238Sodium Iodide2×HCID 8471TriethylamineHCID 703202-Bromomethylnaphthalene2×HCID 516893Potassium Bicarbonate2×HCID 705073103-Methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylic acid

Product 1

HCID 705085482-Naphthylmethyl 3-methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylateYield 84.1%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylic acid (4.48 g., 8.7 mmoles) was dissolved in 30 ml. of dimethylformamide. Triethylamine (8.79 mg., 8.7 mmoles) was added and the mixture stirred for 30 minutes. Potassium bicarbonate (1.74 g., 17.4 mmoles) was added and stirring continued for 1 hour. Finally sodium iodide (1.3 g., 8.7 mmoles) and 2-(bromomethyl)naphthalene (2.11 g., 9.6 mmoles) were added (a slight exotherm was noted), and the mixture allowed to stir about 16 hours at room temperature. Since tlc (9:1 acetone:water) monitoring of the reaction mixture over the next 8 hours indicated that reaction had ceased prior to complete conversion to the ester, one-tenth quantities of potassium bicarbonate, sodium iodide and 2-(bromomethyl)naphthalene were added and the reaction allowed to proceed for a further 16 hours. The reaction mixture was diluted with 1:1 ethyl acetate:water, and the organic layer was separated and back-washed several times with water. The organic phase was layered with fresh water, the pH lowered to 2.5, and the organic layer separated, washed with several portions of water, washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to yield 2-naphthylmethyl 3-methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylate [4.8 g., 84%; Rf 0.39 (ethyl acetate)].

Workup

  1. stirringstirring
  2. waitcontinued for 1 hour
  3. stirringto stir about 16 hours at room temperature
  4. additionwere added
  5. waitto proceed for a further 16 hours
  6. customwater, and the organic layer was separated
  7. washback-washed several times with water
  8. customthe organic layer separated
  9. washwashed with several portions of water
  10. washwashed with brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-9cf0e1dd15db45a5b518e8d5df29890b
Source dataset
uspto-grants-1984_01
Patent number
US04429128

Reaction notes

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