Methoxymethyl-triphenylphosphonium chloride → (Z)-tert-butyl 2-benzyl-4-(methoxymethylene)piperidine-1-carboxylate

HRID 529102Notes

Reaction equation

HRID 529102 reaction equation
CC(C)([O-])C.[K+].[Cl-].[CH3:8][O:9][CH2:10][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:30]([CH:37]1[CH2:42][C:41](=O)[CH2:40][CH2:39][N:38]1[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C1COCC1>[CH2:30]([CH:37]1[CH2:42]/[C:41](=[CH:8]\[O:9][CH3:10])/[CH2:40][CH2:39][N:38]1[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 183199211-Boc-2-benzylpiperidin-4-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 69811901(Z)-tert-butyl 2-benzyl-4-(methoxymethylene)piperidine-1-carboxylateYield 34.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium tert-butoxide (4.49 mL, 1M in THF) was added over about 5 minutes to (methoxymethyl)triphenylphosphonium chloride (1.42 g, 4.15 mmol) suspended in anhydrous THF (25 mL) at 0° C. The resulting suspension was stirred at about this temperature for about 45 minutes at which time, tert-butyl 2-benzyl-4-oxopiperidine-1-carboxylate (1.0 g, 3.46 mmol) dissolved in THF (5 mL) was added. The reaction mixture was allowed to warm to ambient and stir for another 6 h. The reaction was quenched by the addition of ammonium chloride solution and then taken up in EtOAc. After washing twice with water and once with brine, the organic portion was dried over magnesium sulfate, filtered and concentrated. The resulting semi-solid residue was purified via silica gel chromatography to give (Z)-tert-butyl 2-benzyl-4-(methoxymethylene)piperidine-1-carboxylate (375 mg, 34%). LCMS (APCI+) m/z 218.1 [M+H]+; Rt=4.51 min.

Workup

  1. additionwas added
  2. temperatureto warm
  3. customThe reaction was quenched by the addition of ammonium chloride solution
  4. washAfter washing twice with water and once with brine
  5. dry with materialthe organic portion was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting semi-solid residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-5a2ddb01e4d44cff82c3978d0c44bc9d
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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