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4-Toluenesulfonyl chloride → 2-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-tosyloxyprop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 463583
Notes
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Reaction equation

HRID 463583 reaction equation
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[CH2:16]([C:20]1[CH2:27][S:26][CH:25]2[N:22]([C:23](=[O:36])[CH:24]2[NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:21]=1[C:37]([O:39][CH:40]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38])[C:17]([CH3:19])=[O:18].[C:53]1([CH3:63])[CH:58]=[CH:57][C:56]([S:59](Cl)(=[O:61])=[O:60])=[CH:55][CH:54]=1>CCCCCC.O1CCCC1.C(OCC)(=O)C.CN(P(N(C)C)(N(C)C)=O)C>[CH:40]([O:39][C:37]([C:21]1[N:22]2[CH:25]([S:26][CH2:27][C:20]=1[CH:16]=[C:17]([O:18][S:59]([C:56]1[CH:57]=[CH:58][C:53]([CH3:63])=[CH:54][CH:55]=1)(=[O:61])=[O:60])[CH3:19])[CH:24]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[C:23]2=[O:36])=[O:38])([C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 130352,2,6,6-TetramethylpiperidineHCID 132333103-Acetonyl-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-eneHCID 178418339Butyllithium

Product 1

HCID 539916602-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-tosyloxyprop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene
Yield 28.6%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
20 °C

Procedure

A 1.6M solution of butyllithium in hexane (3.44 cc) is added, in the course of 10 minutes, to a solution of 2,2,6,6-tetramethylpiperidine (0.78 g) in tetrahydrofuran (5 cc) at 20° C. The solution is stirred for 10 minutes at 20° C. and then cooled to -70° C. A solution of 3-acetonyl-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (2.54 g) in tetrahydrofuran (6 cc) is then added in the course of 20 minutes, and the mixture is then stirred for 15 minutes at -70° C. Hexamethylphosphorotriamide (7 cc) is added in the course of 3 minutes, followed by a solution of p-toluenesulphonyl chloride (5.23 g) in tetrahydrofuran (7 cc) in the course of 3 minutes. The mixture is stirred for 45 minutes at -70° C., the temperature is then left to rise to 0° C. and the solution is diluted with ethyl acetate (100 cc) and washed successively with a 0.1N solution of citric acid (50 cc), a saturated aqueous solution of sodium bicarbonate (50 cc) and distilled water (100 cc). The organic phase is dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is chromatographed on a column of Merck silica gel (0.06-0.20) (110 g) (diameter of the column: 3 cm; height: 26 cm). Elution is carried out with a 15/80 (by volume) ethyl acetate/cyclohexane mixture (1,200 cc), 60 cc fractions being collected. Fractions 3 to 15 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. This yields the Z form of 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-tosyloxyprop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.94 g) in the form of a hard, pale yellow foam.

Workup

  1. temperaturecooled to -70° C
  2. stirringthe mixture is then stirred for 15 minutes at -70° C
  3. stirringThe mixture is stirred for 45 minutes at -70° C.
  4. waitthe temperature is then left
  5. customto rise to 0° C.
  6. washwashed successively with a 0.1N solution of citric acid (50 cc)
  7. distillationa saturated aqueous solution of sodium bicarbonate (50 cc) and distilled water (100 cc)
  8. dry with materialThe organic phase is dried over sodium sulphate
  9. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C
  10. customThe residue is chromatographed on a column of Merck silica gel (0.06-0.20) (110 g) (diameter of the column
  11. washElution
  12. custombeing collected
  13. concentrationFractions 3 to 15 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C

Sources & evidence

ORD record
ord-4e8eb080714242ae87a995c08534ec0f
Source dataset
uspto-grants-1985_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04520193

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes