2,2,6,6-Tetramethylpiperidine → HCID 60004405, compound

HRID 2184263Notes

Reaction equation

HRID 2184263 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[Si:16]([O:23][CH2:24][C@@H:25]1[C@H:29]2[O:30][C:31]([CH3:34])([CH3:33])[O:32][C@H:28]2[C@H:27]([N:35]2[CH:43]=[N:42][C:41]3[C:36]2=[N:37][CH:38]=[N:39][C:40]=3[Cl:44])[O:26]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].[CH2:45]([Sn:49](Cl)([CH2:54][CH2:55][CH2:56][CH3:57])[CH2:50][CH2:51][CH2:52][CH3:53])[CH2:46][CH2:47][CH3:48].[Cl-].[NH4+].C(=O)([O-])O.[Na+]>O1CCCC1.O>[Si:16]([O:23][CH2:24][C@@H:25]1[C@H:29]2[O:30][C:31]([CH3:34])([CH3:33])[O:32][C@H:28]2[C@H:27]([N:35]2[CH:43]=[N:42][C:41]3[C:36]2=[N:37][C:38]([Sn:49]([CH2:50][CH2:51][CH2:52][CH3:53])([CH2:54][CH2:55][CH2:56][CH3:57])[CH2:45][CH2:46][CH2:47][CH3:48])=[N:39][C:40]=3[Cl:44])[O:26]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:17])[CH3:18]

Participants

9

Reactant 6

HCID 130352,2,6,6-TetramethylpiperidineHCID 15096Tributyltin ChlorideHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 15101786HCID 15101786, compoundHCID 178418339Butyllithium

Product 1

HCID 60004405HCID 60004405, compoundYield 71.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

A solution of 2,2,6,6-tetramethylpiperidine (17.6 g, 125 mmol) in dry tetrahydrofuran (350 ml) was cooled to −50° C., under an atmosphere of nitrogen gas, and treated with n-butyllithium (78 ml, 1.6M solution in hexanes, 125 mmol) over 15 minutes. The reaction mixture was then cooled to −70° C. and a solution of 9-[(3aR,4R,6R,6aR)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-chloro-9H-purine (Bioorg. Med. Chem. Lett., 8, 695-698, (1998)) (11.0 g, 25 mmol) in dry tetrahydrofuran (150 ml) was added, dropwise, keeping the temperature below −70° C. The reaction mixture was stirred for 30 minutes. Tri-n-butyl tin chloride (40.7 g, 125 mmol) was then added to the reaction and the mixture stirred at −70° C. for 30 minutes. A saturated solution of ammonium chloride in water (100 ml) was added to the reaction which was then warmed to 0° C. A saturated aqueous solution of sodium hydrogen carbonate was added (150 ml) and the mixture extracted with ethyl acetate (3×100 ml). The combined organic extracts were washed with brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of hexane:ethyl acetate (95:5, by volume) gradually changing to hexane:ethyl acetate (80:20, by volume) to afford the title compound (13.0 g).

Workup

  1. customthe temperature below −70° C
  2. stirringthe mixture stirred at −70° C. for 30 minutes
  3. temperaturewas then warmed to 0° C
  4. extractionthe mixture extracted with ethyl acetate (3×100 ml)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of hexane:ethyl acetate (95:5, by volume)

Sources & evidence

ORD record
ord-7be8e4a24a7046fa8ef52516e4732d7a
Source dataset
uspto-grants-2005_05
Patent number
US06900309B1

Reaction notes

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