Water → tert-Butyl 4-(3-(6-methylpyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

HRID 1666391Notes

Reaction equation

HRID 1666391 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:21]=[CH:22][CH:23]=2)[CH2:12]P(=O)(OCC)OCC)[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][C:36](=O)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].O>C1COCC1.O1CCOCCOCCOCCOCC1>[CH3:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:21]=[CH:22][CH:23]=2)[CH:12]=[C:36]2[CH2:37][CH2:38][N:33]([C:31]([O:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:32])[CH2:34][CH2:35]2)[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86623900Diethyl 3-(6-methylpyridin-2-yloxy)benzylphosphonate

Product 1

HCID 68950276tert-Butyl 4-(3-(6-methylpyridin-2-yloxy)benzylidene)piperidine-1-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 3633615-Crown-5CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Diethyl 3-(6-methylpyridin-2-yloxy)benzylphosphonate (4.7 g, 14 mmol) from Step 3 and 1,4,7,10,13-pentaoxacyclopentadecane (15-Crown-5, 0.05 mL, 0.28 mmol) were combined in THF (150 mL). Sodium hydride (617 mg, 60% dispersion in mineral oil, 15.4 mmol) was added. The reaction was stirred for 30 min and then a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (3.07 g, 15.4 mmol) in THF (15 mL) was added. After 16 h, water was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×200 mL) and the combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (10-30%, EtOAc:heptane) to afford the title compound (4.4 g, 83% yield) as a thick oil.

Workup

  1. waitAfter 16 h
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×200 mL)
  4. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (10-30%, EtOAc:heptane)

Sources & evidence

ORD record
ord-1928fc4e924647e5a2746aec035dcd9b
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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