4-Bromophenetole → [1-(4-Ethoxy-phenyl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl ester

HRID 511149Notes

Reaction equation

HRID 511149 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].Br[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2(C)CC=CC=C2C2C=CC=CC=2)CCCCC1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][CH:9]1[CH2:10][CH2:11][N:12]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=2)[CH2:13][CH2:14]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 685234-BromophenetoleHCID 723429Tert-butyl (piperidin-4-ylmethyl)carbamateHCID 23676156Sodium t-butoxideHCID 66672255Dicyclohexyl-(1-methyl-2-phenylcyclohexa-2,4-dien-1-yl)phosphane

Product 1

HCID 58576345[1-(4-Ethoxy-phenyl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl esterYield 61.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of piperidin-4-ylmethyl-carbamic acid tert-butyl ester (1.0 g; 4.67 mmol), 1-bromo-4-ethoxy-benzene (1.87 g; 9.33 mmol), tris(dibenzylideneacetone)dipalladium (174 mg; 0.19 mmol), sodium tert-butoxide (524 mg; 4.67 mmol) and 2-(dicyclohexylphosphino)-2-methylbiphenyl (135 mg; 0.37 mmol) in toluene (30 mL) is thoroughly flushed with argon. The reaction mixture is then heated at 70° C. for 17 hours. After dilution with ethyl acetate (50 mL), the suspension is filtered over Celite and the filtrate is washed with aq. sat ammonium chloride (2×25 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue obtained is then further purified by flash column chromatography on silica gel (Ethyl acetate:heptane 25:75) to afford the desired product (963 mg; 2.88 mmol).

Workup

  1. customis thoroughly flushed with argon
  2. filtrationAfter dilution with ethyl acetate (50 mL), the suspension is filtered over Celite
  3. washthe filtrate is washed
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue obtained
  7. customis then further purified by flash column chromatography on silica gel (Ethyl acetate:heptane 25:75)

Sources & evidence

ORD record
ord-001c3d7412484f609c55fbf62e56dd9f
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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