Acetic Acid → 4-[4-(3-Piperidin-1-yl-propoxy)benzyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1434564Notes

Reaction equation

HRID 1434564 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(=O)(O)[O-].[Na+]>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([CH2:15][C:14]2[CH:17]=[CH:18][C:11]([O:10][CH2:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:12][CH:13]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27663244-(3-Piperidin-1-ylpropoxy)benzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 686973194-[4-(3-Piperidin-1-yl-propoxy)benzyl]-piperazine-1-carboxylic acid tert-butyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 4-(3-(piperidin-1-yl)propoxy)benzaldehyde (WO 02/12214 A2) (1.90 g, 7.68 mmol) in dichloromethane (25 ml) was added 1-N tert butoxy carbonyl piperazine (1.57 g, 8.45 mmol) followed by acetic acid (1 ml), and the reaction stirred for 1 hour at room temperature, then treated with sodium triacetoxy borohydride (2 g, 9.61 mmol) and stirred for 16 hours at room temperature. The reaction was then diluted with saturated sodium bicarbonate solution and extracted with dichloromethane. The dichloromethane was then washed sequentially with water and brine, dried over anhydrous sodium sulfate and evaporated in vacuo to yield a residue which was purified using silica gel chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95) to afford the title compound (1.586 g, 50%); MS (ES+), m/e 418 [M+H]+.

Workup

  1. stirringstirred for 16 hours at room temperature
  2. extractionextracted with dichloromethane
  3. washThe dichloromethane was then washed sequentially with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customevaporated in vacuo
  6. customto yield a residue which
  7. customwas purified
  8. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95)

Sources & evidence

ORD record
ord-6bc965e3c5c84fe6903172ba8a23a8c4
Source dataset
uspto-grants-2009_11
Patent number
US07615550B2

Reaction notes

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