Hydrazine → 1-((1R,2S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-yl)thiourea

HRID 46157Notes

Reaction equation

HRID 46157 reaction equation
[Si:1](O[C@H]1C[C@H]2C[C@@H]1C[C@@H]2N1C(=O)C2C(=CC=CC=2)C1=O)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:37]N.[C:39]([N:47]=[C:48]=[S:49])(=O)[C:40]1[CH:45]=C[CH:43]=[CH:42][CH:41]=1.[C:50](=[O:53])([O-])[O-].[K+].[K+]>C(O)C.C(Cl)(Cl)Cl.ClCCl.CO>[Si:1]([O:53][C@H:50]1[CH2:45][C@H:40]2[CH2:41][C@@H:42]1[CH2:43][C@@H:39]2[NH:47][C:48]([NH2:37])=[S:49])([C:14]([CH3:15])([CH3:17])[CH3:16])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 9321HydrazineHCID 11430Potassium CarbonateHCID 68284Benzoyl isothiocyanateHCID 58951233HCID 58951233, compound

Product 1

HCID 589513151-((1R,2S,4R,5S)-5-(tert-Butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-yl)thiourea

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-((1R,2S,4R,5S)-5-(tert- butyldiphenylsilyloxy)bicyclo[2.2.1]-heptan-2-yl)isoindoline-1,3-dione (4.60 g, 9.28 mmol) in ethanol (anhydrous, 100 mL) was added anhydrous hydrazine (0.44 mL, 13.9 mmol). After refluxing under nitrogen for 3 h, the mixture was cooled to ambient temp. The white solid was removed by filtration, and the filtrate was concentrated in vacuo to give an off-white solid, which was stirred with benzoyl isothiocyanate (1.62 mL, 12.1 mmol) in chloroform (100 mL) at ambient temp. overnight. The reaction mixture was diluted with dichloromethane (50 mL) and the solid was removed by filtration. The filtrate was concentrated to give an off-white solid, which was stirred with potassium carbonate (3.85 g, 27.8 mmol) in methanol (100 mL) at ambient temp. for 30 min. The solvents were removed in vacuo, and the residue was partitioned between EtOAc and water. The organic portion was separated, washed with brine, and conc. in vacuo. The residue was purified by flash column chromatography (0 to 60% of EtOAc in hexanes) to give the title compound as a white solid. MS m/z: 425.2 (M+H)+.

Workup

  1. temperatureAfter refluxing under nitrogen for 3 h
  2. customThe white solid was removed by filtration
  3. concentrationthe filtrate was concentrated in vacuo
  4. customto give an off-white solid, which
  5. customthe solid was removed by filtration
  6. concentrationThe filtrate was concentrated
  7. customto give an off-white solid, which
  8. customThe solvents were removed in vacuo
  9. customthe residue was partitioned between EtOAc and water
  10. customThe organic portion was separated
  11. washwashed with brine
  12. customThe residue was purified by flash column chromatography (0 to 60% of EtOAc in hexanes)

Sources & evidence

ORD record
ord-3537c0bd288e42bea2b450056aadc6f2
Source dataset
uspto-grants-2013_09
Patent number
US08541592B2

Reaction notes

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