N,N,N',N'-Tetramethylethylenediamine → tert-butyl 4-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)(hydroxy)methyl)piperidine-1-carboxylate

HRID 1923221Notes

Reaction equation

HRID 1923221 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=1.CN(C)CCN(C)C.C([Li])CCC.[CH:31]([CH:33]1[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]1)=[O:32].[NH4+].[Cl-]>CCCCCC.C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:31]([OH:32])[CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[O:40])[CH2:35][CH2:34]3)[N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=1

Participants

8

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 715006872-Chloro-9-methyl-6-(4-morpholinyl)-9H-purineHCID 178418339Butyllithium

Product 1

HCID 59605210tert-butyl 4-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)(hydroxy)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 4-(2-chloro-9-methyl-9H-purin-6-yl)morpholine (750 mg, 3.0 mmol) and N,N,N′,N′-Tetramethylethylenediamine (0.9816 mL, 6.504 mmol) in tetrahydrofuran (38 mL, 460 mmol) was added 1.6 M of n-butyllithium in hexane (4.065 mL) at −78° C. The resulting orange cloudy mixture was stirred at −78° C. for 45 minutes and at −40° C. for 5 minutes. Tert-butyl 4-formylpiperidine-1-carboxylate (1.261 g, 5.913 mmol) in 2 mL of THF was then added. The resulting yellow mixture was stirred at −78° C. for 1 hour. The reaction was then allowed to warm to room temperature. The reaction was then stirred at room temperature for 20 minutes. The reaction was then poured onto sat. NH4Cl. the product was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by FCC (0-10% MeOH in DCM) to give the title compound as a white foam. LCMS m/z 467.3 (MH+).

Workup

  1. stirringThe resulting yellow mixture was stirred at −78° C. for 1 hour
  2. temperatureto warm to room temperature
  3. stirringThe reaction was then stirred at room temperature for 20 minutes
  4. extractionthe product was extracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by FCC (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-9f9f4bce7a9c4b93b9457a12cc7d5f0c
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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