tert-Butyl 4-oxopiperidine-1-carboxylate → tert-butyl 4-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)piperidine-1-carboxylate

HRID 1946032Notes

Reaction equation

HRID 1946032 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12]P(=O)(OC)OC)[N:8]2[CH3:11])=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[N:3]=1.[Li+].CC([N-]C(C)C)C.[C:33]([N:40]1[CH2:45][CH2:44][C:43](=O)[CH2:42][CH2:41]1)([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:12]=[C:43]3[CH2:44][CH2:45][N:40]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:41][CH2:42]3)[N:8]2[CH3:11])=[C:4]([N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)[N:3]=1

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2724682Lithium diisopropylamideHCID 59605250dimethyl (2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylphosphonate

Product 1

HCID 59606199tert-butyl 4-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)piperidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cold (−78° C.) suspension of dimethyl (2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylphosphonate (0.35 g, 0.93 mmol) in THF (8.0 mL) was added a 2.0M solution of LDA in THF (0.49 mL). The resulting solution was allowed to warm to room temperature before the addition of a solution of 1-Boc-4-piperidone (0.19 g, 0.95 mmol) in THF (3 mL). The reaction mixture was then stirred at room temperature for 2 hours, and partitioned between brine and DCM. The organic layer was isolated, washed with brine, dried over MgSO4 and concentrated. The crude residue was then purified by flash chromatrography (0-75% EtOAc in heptane) to give the title compound (0.38 g, 91%). LCMS m/z: 449.2 (MH+).

Workup

  1. custompartitioned between brine and DCM
  2. customThe organic layer was isolated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude residue was then purified by flash chromatrography (0-75% EtOAc in heptane)

Sources & evidence

ORD record
ord-5fc3e7ba31cc443a8e556adfbd4f92b5
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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