Hydrochloric Acid → HCID 58595093, compound

HRID 891491Notes

Reaction equation

HRID 891491 reaction equation
[Na+].[C:2]([C:5]1[N:6]=[C:7]([N:10]2[CH2:13][CH:12]([S:14][C:15]3[C@H:16]([CH3:29])[C@@H:17]4[C@@H:24]([C@H:25]([OH:27])[CH3:26])[C:23](=[O:28])[N:18]4[C:19]=3[C:20]([O-:22])=[O:21])[CH2:11]2)[S:8][CH:9]=1)(=[O:4])[NH2:3].Cl.[C:31]1(O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CN(C1C=CC=CN=1)C.Cl.C(N=C=NCCCN(C)C)C>O.O1CCCC1.C(#N)C.C(OCC)(=O)C>[C:2]([C:5]1[N:6]=[C:7]([N:10]2[CH2:13][CH:12]([S:14][C:15]3[C@H:16]([CH3:29])[C@@H:17]4[C@@H:24]([C@H:25]([OH:27])[CH3:26])[C:23](=[O:28])[N:18]4[C:19]=3[C:20]([O:22][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[O:21])[CH2:11]2)[S:8][CH:9]=1)(=[O:4])[NH2:3]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 996PhenolHCID 218852-DimethylaminopyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 131725307HCID 131725307, compound

Product 1

HCID 58595093HCID 58595093, compoundYield 36.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of (1R,5S,6S)-2-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid sodium salt (162 mg, 0.36 mmol) (obtained as described in Example 3) in a mixture of water (1-ml) and tetrahydrofuran (1 ml) was added 1 M hydrochloric acid (0.33 ml, 0.36 mmol) at 0° C. The mixture was concentrated under reduced pressure. To a solution of the residue in acetonitrile (10 ml) were added phenol (102 mg, 1.1 mmol), dimethylaminopyridine (22 mg, 0.18 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (139 mg, 0.73 mmol) at room temperature. After stirring the mixture for 30 minutes, further 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (139 mg, 0.73 mmol) was added thereto and the resulting mixture was stirred for 30 minutes. At the end of this time, to the reaction mixture was added ethyl acetate and the organic layer was washed sequentially with dilute hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using ethyl acetate—20% acetonitrile; ethyl acetate—40% acetonitrile; ethyl acetate—60% acetonitrile and ethyl acetate to afford phenyl (1R,5S,6S)-2-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (66 mg, yield 36%) as a colorless powder.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. stirringthe resulting mixture was stirred for 30 minutes
  3. washthe organic layer was washed sequentially with dilute hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-e4e9a2d7f64d4dc69f705a74e1df8d6f
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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