4-tert-Butylcyclohexylamine → Methyl 3-bromo-4-{[(4-tert-butylcyclohexyl)amino]methyl}benzoate

HRID 230015Notes

Reaction equation

HRID 230015 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH2:12]Br)[C:5]([O:7][CH3:8])=[O:6].[C:14]([CH:18]1[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]1)([CH3:17])([CH3:16])[CH3:15].C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH2:12][NH:24][CH:21]1[CH2:22][CH2:23][CH:18]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:19][CH2:20]1)[C:5]([O:7][CH3:8])=[O:6]

Participants

6

Reactant 3

HCID 793964-tert-ButylcyclohexylamineHCID 81531DiisopropylethylamineHCID 10804694Methyl 3-bromo-4-(bromomethyl)benzoate

Product 1

HCID 68840739Methyl 3-bromo-4-{[(4-tert-butylcyclohexyl)amino]methyl}benzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product from Example 224 Step B (assume 4.76 mmol) in 5 mL of N,N-dimethylformamide was added 1.02 mL (5.71 mmol) of 4-tert-butylcyclohexylamine and 1.7 mL (9.76 mmol) of N,N-diisopropylethylamine. The resultant mixture was stirred at ambient temperature for 3 hours, diluted with ethyl acetate and the organic layer washed sequentially with three portions of water and one portion of saturated sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (biotage) using 5% ethyl acetate/hexanes as eluent to provide both the cis isomer and the desired trans isomer. 1H NMR (500 MHz, CD3OD) δ 8.18 (s, 1H), 7.97 (d, 1H, J=8 Hz), 7.58 (d, 1H, J=8 Hz), 3.93 (s, 2H), 3.91 (s, 3H), 2.43-2.37 (m, 1H), 2.08-2.01 (m, 2H), 1.85-1.79 (s, 2H), 1.19-4.99 (m, 5H), 0.86 (s, 9H). HPLC/MS (ESI) m/z (M+H)=384.2 (2.47 min.).

Workup

  1. washthe organic layer washed sequentially with three portions of water and one portion of saturated sodium chloride solution
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography (biotage)
  6. customto provide both the cis isomer
  7. customHPLC/MS (ESI) m/z (M+H)=384.2 (2.47 min.)

Sources & evidence

ORD record
ord-5ec9e8e8275f4437a3ae53e3d1e74b50
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Reaction notes

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