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

HRID 1923213Notes

Reaction equation

HRID 1923213 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-e5ba9c963e5c4f928fbdc4d1fe410e8b
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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