Methanol → N-(7'-Bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalene]-1'-ylidene)-2-methylpropane-2-sulfinamide

HRID 1468228Notes

Reaction equation

HRID 1468228 reaction equation
[CH3:1][C:2]([S:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].[Br:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][C:15]3([CH2:21][CH2:20]3)[C:16]2=O)=[CH:11][CH:10]=1.CO.C([O-])(O)=O.[Na+]>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC.CCOC(C)=O>[Br:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][C:15]3([CH2:21][CH2:20]3)[C:16]2=[N:7][S:5]([C:2]([CH3:4])([CH3:3])[CH3:1])=[O:6])=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 3382465Tert-Butanesulfinamide2×HCID 82277895HCID 82277895, compound2×

Product 1

HCID 86706705N-(7'-Bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalene]-1'-ylidene)-2-methylpropane-2-sulfinamideYield 40%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

Titanium ethoxide (5.9 mL, 28.7 mmol), 2-methyl-2-propanesulfinamide (2.61 g, 21.5 mmol) and 7′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-one (Intermediate 6, 3.6 g, 14.3 mmol) in dry 2-Me THF (80 mL) were heated to 100° C. to give an azeotrope. In total 100 mL 2-Me THF was removed and replaced by new 2-Me THF in 50 mL portions over a period of 4 h. The mixture was refluxed overnight. The azeotropic distillation was continued for 9 h and then more 2-methyl-2-propanesulfinamide (2.61 g, 21.5 mmol) and titanium ethoxide (5.9 mL, 28.7 mmol) were added. In total 90 mL 2-Me THF were removed and replaced by new 2-Me THF in 50 mL portions. The mixture was refluxed overnight and the azeotropic distillation was continued for 6 h. The cooled reaction mixture was added to a mixture of MeOH (105 mL), sat. aq. NaHCO3 (41 mL) and EtOAc (430 mL). The resulting slurry was stirred for 2 h and was then filtered through a mixture of diatomaceous earth and Na2SO4 and concentrated. Some material crystallized from the mixture. The solid was triturated with EtOAc/n-heptane and collected by filtration. The mother liquor was purified by flash silica gel chromatography using CHCl3/MeOH 50:1 as eluent and the obtained product was recrystallized from EtOAc/n-heptane. Combining the obtained solids gave 2.02 g (40% yield) of the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.06 (d, 2 H), 1.14 (s, 9 H), 1.40 (d, 2 H), 1.64-1.84 (m, 2 H), 2.83 (m, 2H), 7.36 (d, 1 H), 7.69 (dd, 1 H), 8.16 (d, 1 H); MS (ES+) m/z 354.0 [M+H]+.

Workup

  1. customto give an azeotrope
  2. customIn total 100 mL 2-Me THF was removed
  3. temperatureThe mixture was refluxed overnight
  4. distillationThe azeotropic distillation
  5. waitwas continued for 9 h
  6. customIn total 90 mL 2-Me THF were removed
  7. temperatureThe mixture was refluxed overnight
  8. distillationthe azeotropic distillation
  9. waitwas continued for 6 h
  10. customThe cooled reaction mixture
  11. filtrationwas then filtered through a mixture of diatomaceous earth and Na2SO4
  12. concentrationconcentrated
  13. customSome material crystallized from the mixture
  14. customThe solid was triturated with EtOAc/n-heptane
  15. filtrationcollected by filtration
  16. customThe mother liquor was purified by flash silica gel chromatography
  17. customthe obtained product was recrystallized from EtOAc/n-heptane

Sources & evidence

ORD record
ord-cb77d1e30bf845c38174cdbaa334ba7f
Source dataset
uspto-grants-2015_04
Patent number
US09000184B2

Reaction notes

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