Diethyl Ether → (s)-2-Methyl-1-((s)-1-phenylethyl)piperidin-4-one

HRID 403505Notes

Reaction equation

HRID 403505 reaction equation
C(C1C(C[C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=C2N=C(C)C=C(C)N2N=1)C.C([Mg]Br)=C.CCOCC.[CH3:31][C@H:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1.O>[CH3:15][C@H:16]1[CH2:17][C:18](=[O:21])[CH2:19][CH2:20][N:39]1[C@H:32]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH3:31]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 758181-Phenethylamine, (-)-HCID 683792244-((2-Ethyl-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)phenolHCID 178418507HCID 178418507, compound

Product 1

HCID 13198301(s)-2-Methyl-1-((s)-1-phenylethyl)piperidin-4-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a flame dried roundbottomflask (E)-but-2-enoic acid methoxy-methyl-amide (Einhorn et al., Synth. Commun. 20 (8), 1105-1112 (1990)) (8.0 g, 61.9 mmol) was dissolved in 150 ml of THF. A 1M solution of vinylmagnesium bromide in Et2O (68.1 ml, 68.1 mmol) was added at 0° C. and then the mixture was stirred for 1 h at rt. (S)-(−)-alpha-methylbenzylamin (15.8 ml, 124 mmol) was added at rt, followed by water (15 ml). The reaction was stirred at rt for 1 h. THF was evaporated and 150 ml of water was added. Then the mixture was extracted three times with CH2Cl2 The organic layer was washed with brine, dried over Na2 SO4 and evaporated. The crude product was purified by flash chromatography (silica gel, 20% EtOAc/cyclohexane) which furnished the (S,S) product as the first fraction (confirmed by x-ray).

Workup

  1. stirringThe reaction was stirred at rt for 1 h
  2. customTHF was evaporated
  3. addition150 ml of water was added
  4. extractionThen the mixture was extracted three times with CH2Cl2 The organic layer
  5. washwas washed with brine
  6. customdried over Na2 SO4
  7. customevaporated
  8. customThe crude product was purified by flash chromatography (silica gel, 20% EtOAc/cyclohexane) which
  9. customfurnished the (S,S) product as the first fraction (confirmed by x-ray)

Sources & evidence

ORD record
ord-a6168759d9774d9e921ad1fdd8afc9d1
Source dataset
uspto-grants-2014_06
Patent number
US08748435B2

Reaction notes

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