Sodium Hydroxide → (3R)-N-Methyl-1-(phenylmethyl)-3-piperidinamine

HRID 919562Notes

Reaction equation

HRID 919562 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15](=O)OC(C)(C)C)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1.CCOC(C)=O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][CH3:15])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 25417446tert-Butyl(1-benzylpiperidin-3-yl)carbamate, (R)-

Product 1

HCID 59418231(3R)-N-Methyl-1-(phenylmethyl)-3-piperidinamineYield 95%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (R)-tert-butyl 1-benzylpiperidin-3-ylcarbamate (300 mg, 1.03 mmol) in THF (5 mL) at −30° C., LiAlH4 (0.77 mL of 2 M solution in THF, 1.5 mmol) was added dropwise under inert atmosphere. After addition the reaction mixture was warmed to rt and then heated to reflux for 2 h. After completion of the reaction, a 20% aq. solution of NaOH solution (5 mL) was added dropwise to the reaction mixture. The reaction mixture was diluted with EtOAc (50 mL) and the suspension was filtered over a short pad of celite. The filtrate was dried over Na2SO4 and concentrated in vacuo to give the titled intermediate (200 mg, 94%). The compound was used in the further steps without purification. LC-MS: m/z [M+1]=205.

Workup

  1. additionAfter addition the reaction mixture
  2. temperatureheated
  3. temperatureto reflux for 2 h
  4. customAfter completion of the reaction
  5. filtrationthe suspension was filtered over a short pad of celite
  6. dry with materialThe filtrate was dried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-09aee45c499a461d8238c05f15ed0923
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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