Allyl bromide → HCID 58573609, compound

HRID 932288Notes

Reaction equation

HRID 932288 reaction equation
[CH:1]([Li])([CH2:3]C)[CH3:2].[Cl:6][C:7]1[CH:8]=[C:9]([C@@H:13]2[C@:18]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([CH3:19])[N:17]([CH:27]([CH3:29])[CH3:28])[C:16](=[O:30])[CH2:15][CH2:14]2)[CH:10]=[CH:11][CH:12]=1.C(Br)C=C>C1COCC1>[CH2:3]([C@@H:15]1[CH2:14][C@H:13]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([Cl:6])[CH:8]=2)[C@:18]([C:20]2[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=2)([CH3:19])[N:17]([CH:27]([CH3:28])[CH3:29])[C:16]1=[O:30])[CH:1]=[CH2:2]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 58573664HCID 58573664, compoundHCID 178418400CID 53628100

Product 1

HCID 58573609HCID 58573609, compoundYield 30.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

sec-Butyllithium (0.8N in cyclohexane, 0.274 mL, 0.219 mmol) was added over a period of one minute to a degassed (Argon bubbled through solution for 10 minutes at RT) solution of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-isopropyl-6-methylpiperidin-2-one (Example 418, Step H, 75 mg, 0.199 mmol) in THF (6 mL) cooled by an acetone-dry ice bath. The cold bath was removed and the reaction equilibrated to room temperature over fifteen minutes. The reaction was stirred at room temperature for 30 minutes. Allyl bromide (1M in THF, 0.219 mL, 0.219 mmol) was added over one minute at room temperature. After two hours the reaction was quenched by addition of saturated aqueous ammonium chloride solution. The organic layer was diluted with ethyl acetate and separated. The aqueous layer was extracted again with ethyl acetate. The combined organic layers were then dried with anhydrous magnesium sulfate and concentrated to afford a faintly orange glass. The diastereomeric products were isolated by chromatography on silica gel (12 g RediSep® pre-packed silica gel column (Teledyne Isco, Lincoln, Nebr.)) eluting with 20 to 80% ethyl acetate gradient in hexane to afford 25 mg of (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-isopropyl-6-methylpiperidin-2-one as the product eluting first on silica gel TLC plate (Rf=0.52 in 3:1 hexane:ethyl acetate eluent) and 25 mg of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-isopropyl-6-methylpiperidin-2-one as the product eluting second on silica gel TLC plate (Rf=0.28 in 3:1 hexane:ethyl acetate eluent).

Workup

  1. customa degassed
  2. temperaturecooled by an acetone-dry ice bath
  3. customThe cold bath was removed
  4. customthe reaction equilibrated to room temperature over fifteen minutes
  5. customAfter two hours the reaction was quenched by addition of saturated aqueous ammonium chloride solution
  6. additionThe organic layer was diluted with ethyl acetate
  7. customseparated
  8. extractionThe aqueous layer was extracted again with ethyl acetate
  9. dry with materialThe combined organic layers were then dried with anhydrous magnesium sulfate
  10. concentrationconcentrated
  11. customto afford a faintly orange glass
  12. customThe diastereomeric products were isolated by chromatography on silica gel (12 g RediSep® pre-packed silica gel column (Teledyne Isco, Lincoln, Nebr.))
  13. washeluting with 20 to 80% ethyl acetate gradient in hexane

Sources & evidence

ORD record
ord-29b26dd21e604d04bc8359aaaebc7d62
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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