N-Boc-(R)-2-(3-(2-(3-pyridinyl)vinyl)-benzyl)morpholine → (R)-2-(3-(2-(3-pyridinyl)ethyl)benzyl)morpholine

HRID 2253000Notes

Reaction equation

HRID 2253000 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]=[CH:22][C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[CH:16]=2)[CH2:9]1)(OC(C)(C)C)=O>C(O)C.[Pd]>[N:25]1[CH:26]=[CH:27][CH:28]=[C:23]([CH2:22][CH2:21][C:17]2[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=2)[CH2:14][C@H:10]2[O:11][CH2:12][CH2:13][NH:8][CH2:9]2)[CH:24]=1

Participants

4

Reactant 1

HCID 67073511N-Boc-(R)-2-(3-(2-(3-pyridinyl)vinyl)-benzyl)morpholine

Product 1

HCID 11500146(R)-2-(3-(2-(3-pyridinyl)ethyl)benzyl)morpholine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

N-Boc-(R)-2-(3-(2-(3-pyridinyl)vinyl)-benzyl)morpholine intermediate (a) was dissolved in ethanol (8 mL), with palladium on charcoal (10% w/w, 5 mg) and stirred at room temperature under an atmosphere of hydrogen (1 balloon containing hydrogen) for 18 hours. The reaction was filtered through a pad of celite, washing with ethanol, and the solution was concentrated in vacuo. The crude material was used in the next step without further purification. N-Boc-(R)-2-(3-(2-(3-pyridinyl)ethyl)-benzyl)morpholine (25 mg), was dissolved in a solution of TFA in dichloromethane (20% v/v, 1 mL total) and stirred at room temperature for 3 hrs. The reaction was then poured through an SCX-2 column and washed with dichloromethane. The column was then washed with ammonia (2N, methanol) and the ammonia washes concentrated in vacuo. The residue was purified by column chromatography (prepacked silica, 1 g; dichloromethane/methanol/ammonium hydroxide, 100:10:1) to obtain the desired product example 48 (R)-2-(3-(2-(3-pyridinyl)ethyl)benzyl)morpholine as a yellow oil (10 mg).

Workup

  1. filtrationThe reaction was filtered through a pad of celite
  2. washwashing with ethanol
  3. concentrationthe solution was concentrated in vacuo
  4. customThe crude material was used in the next step without further purification
  5. dissolutionN-Boc-(R)-2-(3-(2-(3-pyridinyl)ethyl)-benzyl)morpholine (25 mg), was dissolved in a solution of TFA in dichloromethane (20% v/v, 1 mL total)
  6. stirringstirred at room temperature for 3 hrs
  7. additionThe reaction was then poured through an SCX-2 column
  8. washwashed with dichloromethane
  9. washThe column was then washed with ammonia (2N, methanol)
  10. concentrationthe ammonia washes concentrated in vacuo
  11. customThe residue was purified by column chromatography (prepacked silica, 1 g; dichloromethane/methanol/ammonium hydroxide, 100:10:1)

Sources & evidence

ORD record
ord-550e91f5f9ce4ec6a8d219c559c71424
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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