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

HRID 2085716Notes

Reaction equation

HRID 2085716 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-1a46900c89194ad99cb9507f1d7d8406
Source dataset
uspto-grants-2004_04
Patent number
US06720338B2

Reaction notes

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