Hydrochloric Acid → HCID 70475851, compound

HRID 464484Notes

Reaction equation

HRID 464484 reaction equation
[NH2:1][CH:2]1[C:17](=[O:18])[N:4]2[C:5]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[C:6]([CH3:9])[CH2:7][S:8][C@H:3]12.C(OC(OCC)C[N:24]=[C:25]=[N:26][CH:27]1[CH2:32]CCCO1)C.CCOCC.Cl>C(Cl)Cl>[CH3:9][C:6]1[CH2:7][S:8][C@@H:3]2[CH:2]([NH:1][C:25]3[NH:24][CH:32]=[CH:27][N:26]=3)[C:17](=[O:18])[N:4]2[C:5]=1[C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 20263338HCID 20263338, compoundHCID 67894209HCID 67894209, compound

Product 1

HCID 70475851HCID 70475851, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of t-butyl 7-amino-3-methylceph-3-em-4-carboxylate (810 mg.) and 1-(2,2-diethoxyethyl)-3-(tetrahydropyran-2-yl)carbodiimide (726 mg.) in dry CH2Cl2 (8 ml.) under nitrogen at room temperature was dropwise added a 2N ether solution of HCl (1.5 ml.) in CH2Cl2 (4 ml.) over 30 minutes. The mixture was allowed to stand for a further 30 minutes and then evaporated to dryness. To a solution of the residue, t-butyl 7-[2-(2,2-diethoxyethyl)-3-(tetrahydropyran-2-yl)guanidino]-3-methylceph-3-em-4-carboxylate (1.7 g.) in acetonitrile (8 ml.) was added 3N aqueous HCl (1 ml.) and the mixture was heated at 50° for 2 hours, then evaporated to dryness at 30°. The residue was purified by chromatography on silica gel using CH2Cl2 /MeOH/HOAc 89:10:1 v/v/v as eluant to give, after precipitation from CH2Cl2 solution will ether, t-butyl 3-methyl-7-[5-hydroxy-1-(tetrahydropyran-2-yl)imidazolin-2-yl]aminoceph-3-em-4-carboxylate (900 mg.) as a mixture of diastereoisomers. A solution of this product in trifluoroacetic anhydride was allowed to stand at room temperature under nitrogen for 6 hours, and then evaporated to dryness. The residue was purified by chromatography on silica to give t-butyl 3-methyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylate. This compound was treated with trifluoroacetic acid to give the free acid, identical to the product obtained in Example 7.

Workup

  1. customevaporated to dryness
  2. additionTo a solution of the residue, t-butyl 7-[2-(2,2-diethoxyethyl)-3-(tetrahydropyran-2-yl)guanidino]-3-methylceph-3-em-4-carboxylate (1.7 g.) in acetonitrile (8 ml.) was added 3N aqueous HCl (1 ml.)
  3. temperaturethe mixture was heated at 50° for 2 hours
  4. customevaporated to dryness at 30°
  5. customThe residue was purified by chromatography on silica gel
  6. customto give
  7. customafter precipitation from CH2Cl2 solution will ether, t-butyl 3-methyl-7-[5-hydroxy-1-(tetrahydropyran-2-yl)imidazolin-2-yl]aminoceph-3-em-4-carboxylate (900 mg.)
  8. additionas a mixture of diastereoisomers
  9. waitto stand at room temperature under nitrogen for 6 hours
  10. customevaporated to dryness
  11. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-93435e1076734c4e93f457da974a9c08
Source dataset
uspto-grants-1985_10
Patent number
US04547573

Reaction notes

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