HCID 72473816, compound → HCID 68673552, compound

HRID 333286Notes

Reaction equation

HRID 333286 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:15](=[N:17][S:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19])[CH3:16])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH:15]([NH:17][S:18]([C:20]([CH3:21])([CH3:23])[CH3:22])=[O:19])[CH3:16])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

3

Reactant 1

HCID 72473816HCID 72473816, compound

Product 1

HCID 68673552HCID 68673552, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

56 g (149.6 mmol) of 2-Methyl-propane-2-sulfinic acid {1-[1-(3,4-dichloro-phenyl)-cyclohexyl]-ethylidene}-amide was dissolved in 1 L of THF. The solution was chilled to −20° C. and treated with 49 g (190 mmol) of Cp2ZrHCl. The mixture was allowed to warm to rt and left to stir overnight before cooling back to −20° C. and quenching with a saturated solution of NH4Cl. The mixture was warmed to rt extracted with EtOAc (3×). The combined organic layers were washed with H2O, brine and then dried over Na2SO4. All volatiles were then removed under reduced pressure. The resulting mixture was suspended in MTBE and filtered. All volatiles were again removed under reduced pressure to give 54 g (96%) of the title compound as a white solid in >90% chemical purity and was used without further purification. The diastereomeric ratio was determined to be >98% (reverse phase HPLC: Symmetry C18 column; solvent gradiant using H2O:ACN with 0.05% TFA): 1H NMR (300 MHz, CDCl3) δ 7.45-7.41 (m, 2 H), 7.20 (dd, 1 H, J=8.6, 2.3 Hz), 3.34-3.25 (m, 1 H), 3.01 (d, 1 H, J=6.9 Hz), 2.50-2.44 (m, 1 H), 2.23-2.17 (m, 1 H), 1.65-1.48 (m, 5 H), 1.34-1.17 (m, 3 H), 1.13 (s, 9 H), 0.98 (d, 3 H, J=6.6 Hz); 13C NMR (75 MHz, CDCl3) δ 141.9, 132.8, 131.1, 130.6, 130.4, 128.5, 60.6, 56.1, 46.5, 33.7, 33.0, 26.6, 22.8, 22.3, 22.1, 16.8.

Workup

  1. additiontreated with 49 g (190 mmol) of Cp2ZrHCl
  2. temperatureto warm to rt
  3. waitleft
  4. temperaturebefore cooling back to −20° C.
  5. customquenching with a saturated solution of NH4Cl
  6. temperatureThe mixture was warmed to rt
  7. extractionextracted with EtOAc (3×)
  8. washThe combined organic layers were washed with H2O, brine
  9. dry with materialdried over Na2SO4
  10. customAll volatiles were then removed under reduced pressure
  11. filtrationfiltered
  12. customAll volatiles were again removed under reduced pressure

Sources & evidence

ORD record
ord-42fa55c836fc4c62b7167dadf3c41b23
Source dataset
uspto-grants-2014_11
Patent number
US08877975B2

Reaction notes

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