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

HRID 1785788Notes

Reaction equation

HRID 1785788 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 The concentrate
  8. customwas purified by flash column chromatography on silica gel with 9:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-ee46f49013f7401bb1fdac805aada75f
Source dataset
uspto-grants-2009_03
Patent number
US07504512B2

Reaction notes

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