Citric Acid → HCID 88421815, compound

HRID 1197400Notes

Reaction equation

HRID 1197400 reaction equation
N12CCCN=C1CCCCC2.[NH2:12][C@:13]1([NH:39][CH:40]=[O:41])[C:37](=[O:38])[N:15]2[CH:16]([C:21]([O:23][CH:24]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[C:17](=[CH2:20])[CH2:18][S:19][C@H:14]12.[Br:42]C(Br)(C(OCC)=O)C(OCC)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C(OCC)(=O)C>[NH2:12][C@:13]1([NH:39][CH:40]=[O:41])[C:37](=[O:38])[N:15]2[C:16]([C:21]([O:23][CH:24]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])=[C:17]([CH2:20][Br:42])[CH2:18][S:19][C@H:14]12

Participants

7

Reactant 4

HCID 311Citric AcidHCID 69427Propanedioic acid, 2,2-dibromo-, 1,3-diethyl esterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 88421509HCID 88421509, compound

Product 1

HCID 88421815HCID 88421815, compoundYield 69.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1,8-diazabicyclo[5.4.0]undec-7-ene (24 mg) in dry tetrahydrofuran (5 ml) was added over 5 min to a solution of diphenylmethyl 7β-amino-7α-formamido-3-methylenecepham-4-carboxylate (prepared above)(739 mg) in dry tetrahydrofuran (30 ml) containing diethyl dibromomalonate (999 mg) at -70° C. under argon. After 25 min the mixture was added to a mixture of ethyl acetate (150 ml) and 5% (w/v) aqueous citric acid (100 ml). The phases were separated and the organic phase washed with water (3×100 ml), brine (100 ml), then dried (anhyd. MgSO4), filtered and the filtrate evaporated to give a yellow solid. Trituration with dichloromethane (15 ml) followed by filtration provided the title compound (609 mg) as a white solid, m.p. 151°-153° C. (decomp.) (Found: C, 52.33; H, 4.00; N, 8.37; S, 6.50; Br, 15.59%. C22H20N3O4SBr requires C, 52.59; H, 3.98; N, 8.37; S, 6.38; Br, 15.94%). υmax (KBr) 3370, 3280, 3150, 1795, 1720, and 1670 cm-1 ; δH (250 MHz, d8 -THF) (major rotamer) 2.70 (2H, broad s, exch. D2O), 3.46 and 3.58 (2H, ABq, J 16.8 Hz), 4.34 and 4.42 (2H, ABq, J 10.0 Hz), 5.21 (1H, s), 6.95 (1H, s), 7.1-7.6 (10H, m), 8.15 (1H, d, J 1.0 Hz, becomes s on D2O exch.), and 8.17 (1H, broad s, exch. D2O); m/z (positive xenon F.A.B.; 3-nitrobenzyl alcohol-NaOAc) MNa;, 524.

Workup

  1. customThe phases were separated
  2. washthe organic phase washed with water (3×100 ml), brine (100 ml)
  3. dry with materialdried (anhyd. MgSO4)
  4. filtrationfiltered
  5. customthe filtrate evaporated
  6. customto give a yellow solid
  7. filtrationTrituration with dichloromethane (15 ml) followed by filtration

Sources & evidence

ORD record
ord-1bc76e252cdc4085a0c344ff377b9b93
Source dataset
uspto-grants-1994_01
Patent number
US05275816

Reaction notes

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