Potassium tert-butoxide → (2'R,6'S)-3,3''-dimethyl-1'-[2-(1H-pyrazol-4-yl)-ethyl]-1',2',3',4'5',6'-hexahydro-[2,2';6',2'']terpyridine

HRID 1987326Notes

Reaction equation

HRID 1987326 reaction equation
C([N:8]1[CH2:12][C:11]([CH2:13][CH2:14][N:15]2[C@H:20]([C:21]3[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=3)[CH2:19][CH2:18][CH2:17][C@@H:16]2[C:28]2[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:10][NH:9]1)C1C=CC=CC=1.CC([O-])(C)C.[K+]>CS(C)=O.C1COCC1>[CH3:34][C:33]1[C:28]([C@H:16]2[CH2:17][CH2:18][CH2:19][C@@H:20]([C:21]3[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=3)[N:15]2[CH2:14][CH2:13][C:11]2[CH:12]=[N:8][NH:9][CH:10]=2)=[N:29][CH:30]=[CH:31][CH:32]=1

Participants

5

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 86597120(2'R,6'S)-1'-[2-(2-benzyl-1 H-pyrazol-4-yl)-ethyl]-3,3''-dimethyl-1',2',3',4',5',6'-hexahydro-[2,2';6',2'']terpyridine

Product 1

HCID 11417124(2'R,6'S)-3,3''-dimethyl-1'-[2-(1H-pyrazol-4-yl)-ethyl]-1',2',3',4'5',6'-hexahydro-[2,2';6',2'']terpyridineYield 64.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of (2′R,6′S)-1′-[2-(2-benzyl-1 H-pyrazol-4-yl)-ethyl]-3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (0.130 g, 0.288 mmol) in dry DMSO (0.70 mL) and THF (12 mL) was added 4 Å molecular sieve (˜1 g) pre-heated at 140° C., and KOtBu (0.600 g, 5.35 mmol). The solution was bubbled with air (pre-dried by passing through a NaOH column) at room temperature for 1 h. Saturated aqueous NH4Cl (20 mL) was then added. The mixture was filtered through a celite cake and the cake was washed with EtOAc throughout. The organic layer in the filtrate was collected, and the aqueous layer was extracted with CH2Cl2 (3×30 mL). The extracts were combined and dried over Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on a silica gel column (200:10:1 CH2Cl2/CH3OH/NH4OH), affording a pale yellow solid (0.067 g, 64%) after precipitation from CH2Cl2/hexanes by evaporation under vacuum. 1HNMR(CDCl3) δ 1.60-1.85 (4H), 2.00-2.15 (m, 2H), 2.25-2.62 (m, 10H), 4.10-4.20 (m, 2H), 6.73 (s, 2H), 7.07-7.12 (m, 2H), 7.43 (d, 2H, J=7.2 Hz), 8.45 (s, br. 2H); 13C NMR (CD2Cl2) δ 19.02, 21.33, 25.61, 30.31, 50.86, 64.12, 118.85, 122.40, 132.22, 132.65, 138.78, 147.03, 160.46. ES-MS m/z 362 (M+H). Anal. Calcd. for C22H27N5.0.2H2O: C, 72.38; H, 7.56; N, 19.18. Found: C, 72.31; H, 7.70; N, 18.98.

Workup

  1. customThe solution was bubbled with air (
  2. custompre-dried
  3. customat room temperature
  4. customfor 1 h
  5. additionSaturated aqueous NH4Cl (20 mL) was then added
  6. filtrationThe mixture was filtered through a celite cake
  7. washthe cake was washed with EtOAc throughout
  8. customThe organic layer in the filtrate was collected
  9. extractionthe aqueous layer was extracted with CH2Cl2 (3×30 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationAfter filtration the solvent
  12. customwas removed by evaporation under vacuum
  13. customthe residue was purified by flash chromatography on a silica gel column (200:10:1 CH2Cl2/CH3OH/NH4OH)

Sources & evidence

ORD record
ord-b54335a4a9784f199b631c4d305bbc83
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

Loading…