8-Phenyloctan-1-amine → N-(8-Phenyl-octyl)-3,5-bis-(m-chlorophenyl)4-(2-hydroxyethoxy)-benzamide

HRID 1281375Notes

Reaction equation

HRID 1281375 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][CH:34]=[C:33]([Cl:37])[CH:32]=2)[C:28]([O:38][CH2:39][CH2:40][OH:41])=[C:27]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[CH:43]=2)[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:26]=[C:27]([C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[CH:43]=3)[C:28]([O:38][CH2:39][CH2:40][OH:41])=[C:29]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=3)[CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 1455568-Phenyloctan-1-amineHCID 539906423,5-Bis-(m-chlorophenyl)4-(2-hydroxyethoxy)benzoic acid ethyl esterHCID 178418339Butyllithium

Product 1

HCID 22237408N-(8-Phenyl-octyl)-3,5-bis-(m-chlorophenyl)4-(2-hydroxyethoxy)-benzamideYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a flamed dried round bottom flask with 8-phenyloctyl amine (0.484 mL, 2.43 mmol) and THF (5 mL) cooled to 0° C. was added n-BuLi (0.972 mL, 2.5 M in hexane, 2.43 mmol) dropwise over a 5 min. period. The resulting solution was allowed to stir 5 min. and then warmed to room temperature for 30 min. This solution was then added dropwise to a solution of 3,5-bis-(m-chlorophenyl)-4-(2-hydroxyethoxy)benzoic acid ethyl ester (0.300 g, 0.696 mmol) in THF (15 mL) at −20° C. This final mixture was stirred at −20° C. for 15 min and then warmed to room temperature for 15 min. At this point, the reaction mixture was quenched with H2O (10 mL) and diluted with EtOAc (200 mL). The organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (20 to 40% EtOAc/petroleum ether gradient) to afford the product (0.267 g, 65%) as a clear oil; 1H NMR (CDCl3) δ 1.09-1.48 (m, 9H), 1.48-1.72 (m, 4H), 2.58 (t, J=6.8 Hz, 2H), 3.30-3.35 (m, 2H), 3.35-3.41 (m, 2H), 3.46 (dd, J=6.8, 13.0 Hz, 2H), 6.07-6.18 (m, 1H), 7.11-7.19 (m, 3H), 7.21-7.31 (m, 2H), 7.35-7.44 (m, 4H), 7.44-7.57 (m, 2H), 7.63 (s, 2H), 7.77 (s, 2H); mass spectrum [(+) ESI], m/z 590 (M)+.

Workup

  1. temperaturewarmed to room temperature for 30 min
  2. temperaturewarmed to room temperature for 15 min
  3. customAt this point, the reaction mixture was quenched with H2O (10 mL)
  4. additiondiluted with EtOAc (200 mL)
  5. washThe organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationAfter concentration
  8. customthe residue was purified by the Biotage Flash 40 apparatus (20 to 40% EtOAc/petroleum ether gradient)

Sources & evidence

ORD record
ord-e802bbdd5c97422395980b139f849c66
Source dataset
uspto-grants-2002_09
Patent number
US06451827B2

Reaction notes

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