Tributylstannane → (R)-tert-butyl 3-(6-(tributylstannyl)pyrazin-2-ylamino)piperidine-1-carboxylate

HRID 1529311Notes

Reaction equation

HRID 1529311 reaction equation
[CH2:1]([SnH:5]([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].[Li+].CC([N-]C(C)C)C.Cl[C:23]1[N:28]=[C:27]([NH:29][C@@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)[CH:26]=[N:25][CH:24]=1>C1COCC1>[CH2:10]([Sn:5]([CH2:1][CH2:2][CH2:3][CH3:4])([CH2:6][CH2:7][CH2:8][CH3:9])[C:23]1[N:28]=[C:27]([NH:29][C@@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)[CH:26]=[N:25][CH:24]=1)[CH2:11][CH2:12][CH3:13]

Participants

5

Reactant 3

HCID 5948TributylstannaneHCID 2724682Lithium diisopropylamideHCID 54775326(R)-tert-butyl 3-(6-chloropyrazin-2-ylamino)piperidine-1-carboxylate

Product 1

HCID 86709769(R)-tert-butyl 3-(6-(tributylstannyl)pyrazin-2-ylamino)piperidine-1-carboxylateYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-tert-butyl 3-aminopiperidine-1-carboxylate (1.53 g, 7.6 mmol) in DMF (76 mL) was added Et3N (22 mmol) stirred for 15 min. 2-6-Dichloro pyrazine (1.14 g, 76 mmol) was added at RT and the reaction mixture was stirred at 100° C. overnight. The resulting reaction mixture was quenched with ice cold water and precipitate was formed. The precipitate was collected by filtration, washed with ice cold water and dried to obtain (R)-tert-butyl 3-(6-chloropyrazin-2-ylamino)piperidine-1-carboxylate (1.1 g, 43%). MS (ESI, pos. ion) m/z: 313 (M+1). To a solution of tributyltin hydride (1.39 g, 4.8 mmol) in THF (25 mL) at 0° C. was added LDA (1.8 M; 0.5 mL, 4.8 mmol) and stirred at the same temperature for 10 min. (R)-tert-butyl 3-(6-chloropyrazin-2-ylamino)piperidine-1-carboxylate (1.1 g) was added at 0° C. and the reaction mixture was stirred at RT for an additional 3 h. The resulting mixture was quenched with 10% KF aqueous solution and extracted with EtOAc. The organic layer was separated, dried over Na2SO4 and concentrated to dryness. The crude product was purified by column chromatography, using basic alumina, and eluting with 10% EtOAc/hexane to obtain pure (R)-tert-butyl 3-(6-(tributylstannyl)pyrazin-2-ylamino)piperidine-1-carboxylate (0.8 g, 48%). MS (ESI, pos. ion) m/z: 569.2 (M+1).

Workup

  1. additionwas added at 0° C.
  2. customThe resulting mixture was quenched with 10% KF aqueous solution
  3. extractionextracted with EtOAc
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by column chromatography
  8. washeluting with 10% EtOAc/hexane

Sources & evidence

ORD record
ord-0928bd53647a495c867adebc009a6c1f
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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