2,2,6,6-Tetramethylpiperidine → 6-Chloro-9-(tetrahydro-2H-pyran-2-yl)-2-(tributylstannyl)-9H-purine

HRID 421312Notes

Reaction equation

HRID 421312 reaction equation
CC1(C)CCCC(C)(C)N1.[Cl:11][C:12]1[N:20]=[CH:19][N:18]=[C:17]2[C:13]=1[N:14]=[CH:15][N:16]2[CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1.[CH2:27]([Sn:31](CCCC)([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH3:30].[Cl-].[Cl-].[NH4+]>O1CCCC1.C([Li])CCC.C(OCC)(=O)C>[Cl:11][C:12]1[N:20]=[C:19]([Sn:31]([CH2:32][CH2:33][CH2:34][CH3:35])([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:27][CH2:28][CH2:29][CH3:30])[N:18]=[C:17]2[C:13]=1[N:14]=[CH:15][N:16]2[CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1

Participants

8

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 25517Ammonium ChlorideHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 86641992Tetrabutyltin chloride

Product 1

HCID 112263006-Chloro-9-(tetrahydro-2H-pyran-2-yl)-2-(tributylstannyl)-9H-purineYield 80.3%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 178418339ButyllithiumSolvent

Conditions

Temperature
-78 °C

Procedure

2,2,6,6-Tetramethylpiperidine (26.5 ml, 157 mmol) was dissolved in tetrahydrofuran (200 ml) in an argon atmosphere and n-butyl lithium (2.6 M hexane solution, 54 ml) was added dropwise at room temperature. After the completion of dropwise addition, the resulting mixture was stirred for 15 minutes. The reaction mixture was cooled to −78° C. followed by the dropwise addition of a tetrahydrofuran (30 ml) solution of 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (7.5 g, 31.4 mmol) and the resulting mixture was stirred at the same temperature for 40 minutes. Tetrabutyltin chloride (26 ml, 94.3 mmol) was added dropwise to this solution and the resulting mixture was stirred for 30 minutes. An aqueous ammonium chloride solution was added, the resulting mixture was heated to room temperature followed by the addition of ethyl acetate, and the organic layer was fractionated. The organic layer was washed with water and saturated brine and dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=9:1 to 8:2 to 7:3 to 6:4 to 5:5) to give the title compound (13.3 g, 80%) as a pale yellow oil.

Workup

  1. additionwas added dropwise at room temperature
  2. additionAfter the completion of dropwise addition
  3. stirringthe resulting mixture was stirred at the same temperature for 40 minutes
  4. stirringthe resulting mixture was stirred for 30 minutes
  5. temperaturethe resulting mixture was heated to room temperature
  6. washThe organic layer was washed with water and saturated brine
  7. dry with materialdried over magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=9:1 to 8:2 to 7:3 to 6:4 to 5:5)

Sources & evidence

ORD record
ord-2580c2b0773546da8eaec069a0f871d7
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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