Sodium bis(trimethylsilyl)amide → Ethyl 4-(4-methylenepiperidin-1-yl)benzoate

HRID 2356048Notes

Reaction equation

HRID 2356048 reaction equation
[CH3:1][Si](C)(C)[N-][Si](C)(C)C.[Na+].O=[C:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=2)[CH2:14][CH2:13]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH2:1]=[C:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=2)[CH2:14][CH2:13]1

Participants

5

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 12717442Ethyl 4-(4-oxopiperidin-1-yl)benzoate

Product 1

HCID 16109082Ethyl 4-(4-methylenepiperidin-1-yl)benzoate

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

A 0° C. solution of methyltriphenylphosphonium bromide (500 mg, 1.4 mmol) in THF (1.5 mL) was treated dropwise with 1M sodium hexamethyldisilazide in THF (1.4 mL), stirred for 15 minutes, and added dropwise to a 0° C. solution of Example 158B (0.25 g, 1.0 mmol) in THF (2.1 mL). After stirring for 15 minutes, the reaction was quenched with water and was extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 9:1 hexanes/ethyl acetate to provide the desired product. MS (DCI) m/e 246 (M+H)+.

Workup

  1. stirringAfter stirring for 15 minutes
  2. customthe reaction was quenched with water
  3. extractionwas extracted with ethyl acetate
  4. washThe combined extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe concentrate was purified by flash column chromatography on silica gel with 9:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-cba5b25be3c741e1af0538e524a63617
Source dataset
uspto-grants-2010_07
Patent number
US07754886B2

Reaction notes

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