Water → 3-Methylene-piperidine-1-carboxylic acid tert-butyl ester

HRID 2044086Notes

Reaction equation

HRID 2044086 reaction equation
CCCCCC.[Li][CH2:8][CH2:9][CH2:10][CH3:11].O=C1CC[CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1.O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOCC>[CH2:11]=[C:10]1[CH2:9][CH2:8][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1

Participants

7

Reactant 4

HCID 962WaterHCID 8058HexaneHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 112525943-Methylene-piperidine-1-carboxylic acid tert-butyl esterYield 46%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

A 2.5 M hexane solution of n-BuLi (4.86 mL, 12.15 mmol) was added to a suspension of methyltriphenylphosphonium bromide (4.34 g, 12.15 mmol) in Et2O (100 mL) at 0° C. The mixture was stirred at room temperature for 10 min. A solution of tert-butyl 3-oxopiperidine-1-carboxylate (2.2 g, 11.04 mmol) in ether (10 mL) was added dropwise. The resultant mixture was stirred at room temperature for 1 h, at reflux for 30 min, and cooled to room temperature. After the addition of water (30 mL), the two phases were separated. The aqueous phase was extracted with ether (3×60 mL). The combined ether extracts were washed with brine (20 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 0 to 15% ethyl acetate in hexane, gave a colorless liquid (1.0 g, 46%). 1H NMR (400 MHz, chloroform-d) δ ppm 4.61-4.96 (2H, m), 3.87 (2H, s), 3.25-3.55 (2H, m), 2.09-2.39 (2H, m), 1.54-1.73 (2H, m), 1.46 (9H, s).

Workup

  1. temperatureat reflux for 30 min
  2. temperaturecooled to room temperature
  3. customthe two phases were separated
  4. extractionThe aqueous phase was extracted with ether (3×60 mL)
  5. washThe combined ether extracts were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. washSilica gel chromatography, eluting with 0 to 15% ethyl acetate in hexane

Sources & evidence

ORD record
ord-55064c7da2e14cb4b657b138ad641d1f
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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