Acetic Acid → Tert-butyl 4-((2-bromo-5,5-dimethylcyclohex-1-enyl)methyl)piperazine-1-carboxylate

HRID 410340Notes

Reaction equation

HRID 410340 reaction equation
[Br:1][C:2]1[CH2:7][CH2:6][C:5]([CH3:9])([CH3:8])[CH2:4][C:3]=1[CH:10]=O.C(O)(=O)C.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([CH2:10][C:3]2[CH2:4][C:5]([CH3:8])([CH3:9])[CH2:6][CH2:7][C:2]=2[Br:1])[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 251391912-Bromo-5,5-dimethylcyclohex-1-enecarbaldehyde

Product 1

HCID 67422645Tert-butyl 4-((2-bromo-5,5-dimethylcyclohex-1-enyl)methyl)piperazine-1-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-bromo-5,5-dimethyl-cyclohex-1-ene carbaldehyde (1 g, 4.61 mmol) in dichloromethane (70 ml) at rt under nitrogen was added glacial acetic acid (0.29 ml, 5.1 mmol) followed by piperazine-1-carboxylic acid tert-butyl ester (0.94 g, 5.07 mmol). The reaction was stirred for 1 h before sodium triacetoxyborohydride (2.05 g, 9.68 mmol) was introduced. After 16 h, a solution of 5% NaOH (20 ml) was added and the mixture was extracted with dichloromethane. The organic layer was separated and washed with H2O, dried (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. Purification by column chromatography on silica eluting with 5% EtOAc/heptane provided 4-(2-bromo-5,5-dimethyl-cyclohex-1-enylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (1.3 g, 73%).-1H NMR (MeOD) δ 3.44 (4H, br t), 3.14 (2H, br s), 2.55 (2H, br m), 2.40 (4H, br t), 2.08 (2H, br s), 1.51 (2H, t), 1.48 (9H, s), 0.93 (6H, s).

Workup

  1. additionwas introduced
  2. extractionthe mixture was extracted with dichloromethane
  3. customThe organic layer was separated
  4. washwashed with H2O
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product
  9. customPurification by column chromatography on silica eluting with 5% EtOAc/heptane

Sources & evidence

ORD record
ord-dc9c4351f6e2462ba08a73f4ded1809d
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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