Tributylstannane → 2-Cyclopropyl-7-[(1S*,3R*)-3-hydroxycyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17590Notes

Reaction equation

HRID 17590 reaction equation
[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:27]#[N:28])[C:10]([CH3:26])=[C:11]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:12]=3[C@H:13]3[CH2:17][C@H:16](I)[C@@H:15]([OH:19])[CH2:14]3)[N:8]=2)[CH2:3][CH2:2]1.N(C(C)(C)C#N)=NC(C)(C)C#N.C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:27]#[N:28])[C:10]([CH3:26])=[C:11]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:12]=3[C@H:13]3[CH2:17][CH2:16][C@@H:15]([OH:19])[CH2:14]3)[N:8]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 5948Tributylstannane2×HCID 6547AzobisisobutyronitrileHCID 685864492-Cyclopropyl-7-[(1R*,3S*,4S*)-3-hydroxy-4-iodocyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Product 1

HCID 685843982-Cyclopropyl-7-[(1S*,3R*)-3-hydroxycyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 60%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2-Cyclopropyl-7-[(1R*,3S*,4S*)-3-hydroxy-4-iodocyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-301) (240 mg, 0.50 mol) was dissolved in toluene (4.8 ml), then at room temperature, 2,2′-azobisisobutyronitrile (8 mg, 0.05 mmol) and tri-n-butyltin hydride (180 μl, 0.64 mmol) were added. The solution was heated under reflux under nitrogen atmosphere for 3 hours. Monitoring the reaction by TLC showed the remaining starting material, and the solution was cooled to room temperature and tri-n-butyltin hydride (89 μl, 0.32 mmol) was again added. After further heated under reflux for 1 hour, this was cooled to room temperature. The solvent was evaporated away under reduced pressure, and the resulting residue was combined with the entitled compound (I-302) separately synthesized according to a different method, and purified by middle-pressure liquid chromatography (eluent, n-hexane:ethyl acetate=1:1, v/v) to obtain the entitled compound (113 mg, 60%) as a colorless gel.

Workup

  1. temperatureThe solution was heated
  2. temperatureunder reflux under nitrogen atmosphere for 3 hours
  3. customMonitoring the reaction by TLC
  4. temperatureAfter further heated
  5. temperatureunder reflux for 1 hour
  6. temperaturethis was cooled to room temperature
  7. customThe solvent was evaporated away under reduced pressure
  8. customseparately synthesized
  9. custompurified by middle-pressure liquid chromatography (eluent, n-hexane

Sources & evidence

ORD record
ord-e00bfb51cff6485289adf40101d1cf3d
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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