Hydrochloric Acid → HCID 131714959, compound

HRID 1731695Notes

Reaction equation

HRID 1731695 reaction equation
C(C1C=NC=CC=1)#C.C([Li])CCC.[S].[Li][S:16][C:17]#[C:18][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1.[NH2:25][C:26]1[S:30][N:29]=[C:28]([C:31](=[N:62][O:63][CH2:64][CH3:65])[C:32]([NH:34][CH:35]2[C:60](=[O:61])[N:37]3[C:38]([C:44]([O:46][CH:47]([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)=[O:45])=[C:39]([CH2:42]I)[CH2:40][S:41][C@H:36]23)=[O:33])[N:27]=1.Cl>O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C.O.C(OCC)(=O)C>[NH2:25][C:26]1[S:30][N:29]=[C:28]([C:31](=[N:62][O:63][CH2:64][CH3:65])[C:32]([NH:34][CH:35]2[C:60](=[O:61])[N:37]3[C:38]([C:44]([O:46][CH:47]([C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=4)[C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)=[O:45])=[C:39]([CH2:42][S:16][C:17]#[C:18][C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH2:40][S:41][C@H:36]23)=[O:33])[N:27]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 1860033-EthynylpyridineHCID 5362487SulfurHCID 131714960HCID 131714960, compoundHCID 178418339ButyllithiumHCID 178506963HCID 178506963, compound

Product 1

HCID 131714959HCID 131714959, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of 3-ethynylpyridine (258 mg) in a mixture of tetrahydrofuran (7 ml) and hexamethylphosphoric triamide (0.3 ml) was dropwise added n-butyllithium (1.55M in hexane) (1.3 ml) at -30° C. Sulfur (72 mg) was added to the reaction mixture at -25° C. at once. The mixture was stirred for 30 minutes under ice-cooling and then allowed to warm to 15° C. to give a solution containing 3-(2-lithiothioethynyl)pyridine. This solution was added to a solution of benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-iodomethyl-3-cephem-4-carboxylate (syn isomer) (1.4 g) in tetrahydrofuran (20 ml) at -50° C. The mixture was stirred for 40 minutes at -50° C. To the mixture was added 6N hydrochloric acid (1 ml) at -60° C. The mixture was warmed up to ambient temperature. To the mixture was added a mixture of ethyl acetate and water. The separated organic layer was dried over sodium sulfate, concentrated in vacuo, and the residue was triturated in diisopropyl ether to give a solid. The solid was subjected to column chromatography on silica gel (15 g) eluting with a mixture of ethyl acetate and n-hexane (1:1 (V/V), 4:1 (V/V)). The fractions containing the object compound were combined, concentrated in vacuo, and the residue was triturated in diethyl ether to give benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)ethynylthiomethyl]-3-cephem-4-carboxylate (syn isomer) (576 mg).

Workup

  1. customat -30° C
  2. temperaturecooling
  3. customto give a solution
  4. stirringThe mixture was stirred for 40 minutes at -50° C
  5. temperatureThe mixture was warmed up to ambient temperature
  6. additionTo the mixture was added
  7. dry with materialThe separated organic layer was dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customthe residue was triturated in diisopropyl ether
  10. customto give a solid
  11. washeluting with a mixture of ethyl acetate and n-hexane (1:1 (V/V), 4:1 (V/V))
  12. additionThe fractions containing the object compound
  13. concentrationconcentrated in vacuo
  14. customthe residue was triturated in diethyl ether

Sources & evidence

ORD record
ord-74fa0a4a1a0b44c58904a9d4e05dc36f
Source dataset
uspto-grants-1986_11
Patent number
US04622318

Reaction notes

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