Chloroform → [[4-[2-(1-ethyl-4,5-dihydro-1H-imidazol-2-yl)ethyl]-1-piperidinyl]methylene]amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid hydrochloride

HRID 364737Notes

Reaction equation

HRID 364737 reaction equation
CO[CH:3](OC)[N:4]1[CH2:9][CH2:8][CH:7]([CH2:10][CH2:11][C:12]2[N:13]([CH2:17][CH3:18])[CH2:14][CH2:15][N:16]=2)[CH2:6][CH2:5]1.[CH3:21][C:22]1([CH3:34])[S:26][C@@H:25]2[C@H:27](N)[C:28](=[O:29])[N:24]2[C@H:23]1[C:31]([OH:33])=[O:32].C([N:38](C(C)C)CC)(C)C.C(Cl)(Cl)[Cl:45]>>[ClH:45].[CH2:17]([N:13]1[CH2:14][CH2:15][N:16]=[C:12]1[CH2:11][CH2:10][CH:7]1[CH2:6][CH2:5][N:4]([CH:3]=[N:38][C:23]2([C:31]([OH:33])=[O:32])[C:22]([CH3:34])([CH3:21])[S:26][CH:25]3[N:24]2[C:28](=[O:29])[CH2:27]3)[CH2:9][CH2:8]1)[CH3:18]

Participants

5

Reactant 4

HCID 6212Chloroform2×HCID 110826-Aminopenicillanic acidHCID 81531DiisopropylethylamineHCID 202397444-[2-(1-Ethyl-4,5-dihydro-imidazol-2-yl)ethyl]-1-piperidine carboxaldehyde dimethylacetal

Product 1

HCID 131714826[[4-[2-(1-ethyl-4,5-dihydro-1H-imidazol-2-yl)ethyl]-1-piperidinyl]methylene]amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid hydrochlorideYield 35%

Conditions

Temperature
0 °C

Procedure

A solution of 4-[2-(1-ethyl-4,5-dihydro-imidazol-2-yl)ethyl]piperidine (0.66 g, 0.0031M) in methanol (6 ml) and dimethylformamide dimethylacetal (6 ml) was heated at 90° C. for 6 hrs. Removal of the excess of dimethylformamide dimethylacetal gave 4-[2-(1-ethyl-4,5-dihydro-imidazol-2-yl)ethyl]-1-piperidine carboxaldehyde dimethylacetal. The solution of the piperidine carboxaldehyde dimethylacetal in chloroform (5 ml) was then added to a mixture of 6-aminopenicillanic acid (0.6 g, 0.0028M) and diisopropylethylamine (0.5 ml) in chloroform (6 ml) at 0° C. The reaction was stirred at 0° C. for 1 hr and room temperature for 3 hrs. The solvent was removed and water (10 ml) was added. After being washed with ethylacetate, the aqueous solution, acidified from about pH 3 to about 3.5 was purified on Sephadex LH 20 columns to give [2S-(2alpha,5alpha,6beta)] -6-[[[4-[2-(1-ethyl-4,5-dihydro-1H-imidazol-2-yl)ethyl]-1-piperidinyl]methylene]amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid hydrochloride (0.46 g, 35% yield).

Workup

  1. customThe solvent was removed
  2. additionwater (10 ml) was added
  3. washAfter being washed with ethylacetate
  4. customwas purified on Sephadex LH 20 columns

Sources & evidence

ORD record
ord-6867850e8af4479aa42285824cf76b06
Source dataset
uspto-grants-1986_08
Patent number
US04605744

Reaction notes

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