Tert-Butanesulfinamide → N-(5'-Bromo-4-(trifluoromethyl)spiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 1965147Notes

Reaction equation

HRID 1965147 reaction equation
[CH3:1][C:2]([S:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].[Br:8][C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][C:14]3([CH2:23][CH2:22][CH:21]([C:24]([F:27])([F:26])[F:25])[CH2:20][CH2:19]3)[C:15]2=O)=[CH:11][CH:10]=1>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:8][C:9]1[CH:17]=[C:16]2[C:12](=[CH:11][CH:10]=1)[CH2:13][C:14]1([CH2:19][CH2:20][CH:21]([C:24]([F:25])([F:26])[F:27])[CH2:22][CH2:23]1)[C:15]2=[N:7][S:5]([C:2]([CH3:4])([CH3:3])[CH3:1])=[O:6]

Participants

4

Reactant 2

HCID 3382465Tert-ButanesulfinamideHCID 679795566'-Bromo-4-(trifluoromethyl)spiro[cyclohexane-1,2'-inden]-1'(3'H)-one2×

Product 1

HCID 67979375N-(5'-Bromo-4-(trifluoromethyl)spiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamideYield 18%

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

Titanium ethoxide (2.03 mL, 9.85 mmol), 2-methyl-2-propanesulfinamide (0.895 g, 7.39 mmol) and 6′-bromo-4-(trifluoromethyl)spiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 78, 1.71 g, 4.93 mmol) in dry 2-Me THF (30 mL) were heated to 100° C. to give an azeotrope at 74° C. The azeotropic distillation was continued for 5 h and then the mixture was refluxed for 2 days. The mixture was cooled to r.t. Water (10 mL) and EtOAc (20 mL) were added, under continuous stirring, while a solid formed. The reaction mixture was stirred at r.t. for 2 h, and then the formed solid was left to sediment for 1 h. The mixture was filtered, and the solid was washed with EtOAc. The filtrate was concentrated in vacuo to give a residue that was purified by flash chromatography (eluent heptane/EtOAc 65/35) to give the title compound (400 mg, 18% yield): 1H NMR (400 MHz, CDCl3) δ ppm 1.34-1.37 (m, 9 H) 1.56 (s, 4 H) 1.73-1.82 (m, 2 H) 2.13 (br. s., 5 H) 2.89 (d, 2 H) 7.22 (d, 1 H) 7.60 (dd, 1 H) 8.53 (d, 1 H); MS (ES+) 451 [M+H]+.

Workup

  1. customto give an azeotrope at 74° C
  2. distillationThe azeotropic distillation
  3. temperaturethe mixture was refluxed for 2 days
  4. additionWater (10 mL) and EtOAc (20 mL) were added, under continuous stirring, while a solid
  5. customformed
  6. waitthe formed solid was left
  7. waitto sediment for 1 h
  8. filtrationThe mixture was filtered
  9. washthe solid was washed with EtOAc
  10. concentrationThe filtrate was concentrated in vacuo
  11. customto give a residue that
  12. customwas purified by flash chromatography (eluent heptane/EtOAc 65/35)

Sources & evidence

ORD record
ord-cacbbc0f3de94f9bbec0c49fcbba9121
Source dataset
uspto-grants-2013_04
Patent number
US08415483B2

Reaction notes

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