Tetrahydrofuran → HCID 131719945, compound

HRID 977639Notes

Reaction equation

HRID 977639 reaction equation
CN(C)C([C@@H]1C[C@H](S)[CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)=[O:12])=O.[CH:25]([N-:28][CH:29]1CCCC[CH2:30]1)(C)[CH3:26].Br[Mg+].C(N(CC)C(C1C=CC=CC=1[S:48]([C:50]1[C@H:51]([CH3:74])[C@@H:52]2[C@@H:69]([C@H:70]([OH:72])[CH3:71])[C:68](=[O:73])[N:53]2[C:54]=1[C:55]([O:57][CH2:58][C:59]1[CH:64]=[CH:63][C:62]([N+:65]([O-:67])=[O:66])=[CH:61][CH:60]=1)=[O:56])=O)=O)C.[Cl-].[NH4+].[O:79]1[CH2:83][CH2:82][CH2:81][CH2:80]1>O>[CH2:25]([N:28]([CH2:29][CH3:30])[C:83]([C@H:82]1[N:6]([C:11]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=2)=[O:12])[CH2:7][C@@H:80]([S:48][C:50]2[C@H:51]([CH3:74])[C@@H:52]3[C@@H:69]([C@H:70]([OH:72])[CH3:71])[C:68](=[O:73])[N:53]3[C:54]=2[C:55]([O:57][CH2:58][C:59]2[CH:60]=[CH:61][C:62]([N+:65]([O-:67])=[O:66])=[CH:63][CH:64]=2)=[O:56])[CH2:81]1)=[O:79])[CH3:26]

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran3×HCID 25517Ammonium ChlorideHCID 10871907(2S,4S)-2-(dimethylaminocarbonyl)-4-mercapto-1-(p-nitrobenzyloxycarbonyl)-1-pyrrolidineHCID 57036270HCID 57036270, compoundHCID 178456742HCID 178456742, compound

Product 1

HCID 131719945HCID 131719945, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3 ml of a tetrahydrofuran solution containing 347 mg (0.982 mmol) of (2S,4S)-dimethylcarbamoyl-1-(4-nitrobenzyloxycarbonyl)-4-mercaptopyrrolidine were cooled in an ice bath, and then 0.97 ml (0.97 mmol) of a tetrahydrofuran solution containing 1M of bromo-magnesium isopropylcyclohexylamide were added dropwise to the cooled solution over a period of 4 minutes, after which the mixture was stirred for 10 minutes. 2 ml of a tetrahydrofuran solution containing 464 mg of the crude 4-nitrobenzyl (1R,5S,6S)-2-(2-diethylcarbamoylphenylsulfinyl)-1-methyl-6-[1(R)-hydroxyethyl]-1-carbapen-2-em-3-carboxylate prepared as described in step (a) above was then added to the solution, and the resulting solution was stirred for a further 30 minutes. At the end of this time, a saturated aqueous solution of ammonium chloride was added, followed by water, and then the reaction mixture was extracted with ethyl acetate 3 times. The organic layers were collected, combined and washed with water and then with a saturated aqueous solution of sodium chloride. The solvent was then removed by distillation under reduced pressure, and the resulting oily residue was subjected to column chromatography through 50 g of silica gel. Elution with a 1:9 by volume mixture of methanol and ethyl acetate afforded 365 mg of the title compound as a foam-like solid (a yield of 62% in terms of the compound of Example 37).

Workup

  1. temperaturewere cooled in an ice bath
  2. additionwere added dropwise to the cooled solution over a period of 4 minutes
  3. customprepared
  4. additionabove was then added to the solution
  5. stirringthe resulting solution was stirred for a further 30 minutes
  6. extractionthe reaction mixture was extracted with ethyl acetate 3 times
  7. customThe organic layers were collected
  8. washwashed with water
  9. customThe solvent was then removed by distillation under reduced pressure
  10. washElution with a 1:9
  11. additionby volume mixture of methanol and ethyl acetate

Sources & evidence

ORD record
ord-c376cf08938843f08ecaaebd65177b85
Source dataset
uspto-grants-1997_03
Patent number
US05614624

Reaction notes

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