8-Phenyloctan-1-amine → N-(8-Phenyloctyl)4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzamide

HRID 1281404Notes

Reaction equation

HRID 1281404 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.C([O:23][C:24](=O)[C:25]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[C:33]([Cl:38])[CH:32]=2)[C:28]([O:39][CH2:40][CH2:41][OH:42])=[C:27](Br)[CH:26]=1)C>C1COCC1>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:24](=[O:23])[C:25]2[CH:30]=[C:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[C:33]([Cl:38])[CH:32]=3)[C:28]([O:39][CH2:40][CH2:41][OH:42])=[CH:27][CH:26]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 1455568-Phenyloctan-1-amineHCID 541260063-Bromo-4-(2-hydroxyethoxy)-5-(3-chloro4-fluorophenyl)benzoic acid ethyl esterHCID 178418339Butyllithium

Product 1

HCID 22237531N-(8-Phenyloctyl)4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzamideYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a flamed dried round bottom flask charged with 8-phenyloctylamine (688 mg, 3.35 mmol, 6.68 μL) in 5 mL THF at −78° C. was added n-BuLi (2.2 mL, 4.4 mmol) as a solution in hexanes. The solution was stirred at −78° C. for 30 min then stirred at room temperature for 15 min. The solution was cooled back down to−40° C. and a cooled (−40° C.) solution of 3-bromo-4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzoic acid ethyl ester (400 mg, 0.957 mmol) in 10 mL THF via cannula. After the addition was completed, the reaction was warmed up to room temperature, stirred for 10 min, then worked up as in Step 2 of Example 135. The crude yellow oil that was obtained was dissolved in 1:1 EtOAc/Hexanes and filtered through a pad of silica gel with the same solvent system to yield 200 mg, 43% of the amide as a yellow oil. 1H NMR (CDCl3) δ 1.25-1.40 (m, 2H); 1.54-1.65 (m, 2H); 1.80 (bs, 1H); 2.57 (t, J=8.18 Hz, 2H); 3.41 (q, J=6.54 Hz, 2H); 3.90 (t, J=6.13, 2H); 4.12 (t, J=6.13 Hz, 2H); 6.07 (m, 1H); 6.99 (d, J=8.13 Hz, 1H); 7.08-7.18 (m, 3H); 7.20-7.27 (m, 2H); 7.33-7.40 (m, 1H); 7.56 (dd, J=6.54 Hz, 3.27 Hz, 1H); 7.65-7.69 (m, 1H); 7.73 (dd, J=8.13 Hz, 2.58 Hz, 1H).

Workup

  1. customTo a flamed dried round bottom flask
  2. stirringthen stirred at room temperature for 15 min
  3. temperatureThe solution was cooled back down to−40° C.
  4. additionAfter the addition
  5. temperaturethe reaction was warmed up to room temperature
  6. stirringstirred for 10 min
  7. customThe crude yellow oil that was obtained
  8. filtrationfiltered through a pad of silica gel with the same solvent system

Sources & evidence

ORD record
ord-f3c418b0ca33417fa6cc95041de74e18
Source dataset
uspto-grants-2002_09
Patent number
US06451827B2

Reaction notes

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