tert-Butyl 4-oxopiperidine-1-carboxylate → 1-Boc-4-Methylenepiperidine

HRID 1162083Notes

Reaction equation

HRID 1162083 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].O=C1CC[N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.CCCCCC>[CH2:4]=[C:3]1[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:1][CH2:2]1

Participants

6

Reactant 2

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 27568081-Boc-4-MethylenepiperidineYield 59%

Reagents, catalysts & solvents 3

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of methyl triphenylphosphonium bromide (2.69 g, 7.5 mmol) in THF (20 mL) was n-butyllithium (1.8 M; 4.2 mL, 7.5 mmol) in hexane slowly added at −78° C. The mixture was stirred for 1 h. After this time, a solution of tert-butyl 4-oxopiperidine-1-carboxylate (1 g, 5.0 mmol) in THF (10 mL) was added dropwise to the mixture. The resultant mixture was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with isohexane (×3). The combined isohexane layers were evaporated and filtrated through a silica-plug. The crude product was purified using flash chromatography with DCM as eluent yielding 0.58 g (59%) of the title compound. HPLC purity 91%, RT=2.47 min (System A; 10-97% MeCN over 3 min); 86%, RT=2.43 min (System B; 10-97% MeCN over 3 min). 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 9H) 2.12-2.22 (m, 4H) 3.35-3.46 (m, 4H) 4.73 (s, 2H). MS (ESI+) for C11H19NO2 m/z 142 (M-C4H8)+. *Previously reported in J. Med. Chem. 2002, 45, 3143-3160.

Workup

  1. additionslowly added at −78° C
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with isohexane (×3)
  4. customThe combined isohexane layers were evaporated
  5. filtrationfiltrated through a silica-plug
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-c2b559c23a434f7aab74bd168abe9713
Source dataset
uspto-grants-2010_10
Patent number
US07820675B2

Reaction notes

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