Acetic Acid → 4-Biphenyl-2-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 410334Notes

Reaction equation

HRID 410334 reaction equation
[C:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:2]([CH:7]=O)=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 121052(1,1'-Biphenyl)-2-carboxaldehydeHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 467430664-Biphenyl-2-ylmethyl-piperazine-1-carboxylic acid tert-butyl esterYield 102.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of biphenyl-2-carbaldehyde (5.01 g, 27.5 mmol) in dichloromethane (150 ml) at rt under nitrogen was added piperazine-1-carboxylic acid tert-butyl ester (5.63 g, 30.2 mmol) followed by glacial acetic acid (1.90 ml, 33.2 mmol). The reaction was stirred for 1 h before sodium triacetoxyborohydride (11.65 g, 55.0 mmol) was introduced. After 3 h, a solution of 5% NaOH (˜15 ml) was added and the mixture was extracted with dichloromethane. The organic layer was separated, washed with H2O (×2), brine, dried (Na2SO4), filtered and concentrated under reduced pressure to give 4-biphenyl-2-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester as an oil (9.9 g, 100%) which was used without further purification. HPLC-MS 353 [M+1]+.

Workup

  1. additionwas introduced
  2. extractionthe mixture was extracted with dichloromethane
  3. customThe organic layer was separated
  4. washwashed with H2O (×2), brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a9e9805d699e4651ad2b46ba8b348e25
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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