Fluoren-9-amine → 9-Fluorenyl 3-methyl-7beta-phenoxyacetamidoceph-3-em-4-carboxylate

HRID 1657394Notes

Reaction equation

HRID 1657394 reaction equation
[CH3:1][C:2]1[CH2:3][S:4][C@@H:5]2[C@H:12]([NH:13][C:14](=[O:23])[CH2:15][O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11](=[O:24])[N:6]2[C:7]=1[C:8]([OH:10])=[O:9].N[CH:26]1[C:38]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[C:32]2[C:27]1=[CH:28][CH:29]=[CH:30][CH:31]=2.N(OCC(C)C)=O>ClCCl>[CH3:1][C:2]1[CH2:3][S:4][C@@H:5]2[C@H:12]([NH:13][C:14](=[O:23])[CH2:15][O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:11](=[O:24])[N:6]2[C:7]=1[C:8]([O:10][CH:26]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:32]=2[C:33]2[C:38]1=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:9]

Participants

5

Reactant 3

HCID 10671Fluoren-9-amineHCID 10958Isobutyl nitriteHCID 111318273-Methyl-7beta-phenoxyacetamidoceph-3-em-4-carboxylic acid

Product 1

HCID 681340739-Fluorenyl 3-methyl-7beta-phenoxyacetamidoceph-3-em-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Methyl-7β-phenoxyacetamidoceph-3-em-4-carboxylic acid (3.48 g., 10 m. moles) was dissolved with 9-aminofluorene (17.5 m moles) in dichloromethane (50 ml) together with isobutyl nitrite (3.62 g., 35 m. moles) and warmed at 35° for 18 hours. The reaction mixture was worked up as described in Example 7 except that a small quantity of ester (0.24, 0.48 m. moles) was filtered from the solution after the acid aqueous wash. On removal of the solvent the crystalline ester was slurried with warm isopropanol (50 ml), cooled and filtered to give the previously unreported title compound (2.60 g) m.pt. 214°, pure by t.l.c. Together with the previously filtered solid the weight of ester isolated represents a 56.8% yield based on the input acid. An analytical sample of the ester crystallised from acetone-methanol had m.pt. 221° - 222.5°; ν max (1% CHBr3 solution) 3390 (--NHCO--), 1778 (β-lactam) 1718 (αβ-unsaturated ester), 1688 + 1520 cm-1 (amide carbonyl); τ (8% CDCl3 solution) 2.2 - 3.2 (complex, phenoxy ring + (--NHCO--) + fluorenyl 9-C + fluorenyl ring), 5.47 (singlet, phenoxy methylene acetamido group, H2), 4.20 (doublet of doublets, J 10, 5 Hz, C-7, H), 5.04 (doublet, J 5 Hz, C-6, H), 6.45 + 6.89 (two doublets [branches of a quartet], J 18 Hz, H2), 7.84 (singlet, C-3, H3). Found C, 67.68; H, 4.64; N, 5.47. C29H24N2O5S requires C, 67.97; H, 4.72; N, 5.47%.

Workup

  1. temperaturewarmed at 35° for 18 hours
  2. filtrationwas filtered from the solution after the acid aqueous wash
  3. customOn removal of the solvent the crystalline ester
  4. temperaturecooled
  5. filtrationfiltered

Sources & evidence

ORD record
ord-a721f99bdcc44916ac838677be764d34
Source dataset
uspto-grants-1976_06
Patent number
US03960843

Reaction notes

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