Acetaldehyde → (2S,4R)-4-Chloro-N-ethyl-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-benzamide

HRID 1785931Notes

Reaction equation

HRID 1785931 reaction equation
[NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[O:13])[C@@H:4]([CH3:22])[CH2:3]1.[CH:23](=O)[CH3:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)C(C)C)(C)C.[Cl:49][C:50]1[CH:58]=[CH:57][C:53]([C:54](Cl)=[O:55])=[CH:52][CH:51]=1>ClCCl>[Cl:49][C:50]1[CH:58]=[CH:57][C:53]([C:54]([N:1]([CH2:23][CH3:24])[C@H:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([C:12](=[O:13])[C:14]3[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=3)[C@@H:4]([CH3:22])[CH2:3]2)=[O:55])=[CH:52][CH:51]=1

Participants

7

Reactant 5

HCID 177AcetaldehydeHCID 85014-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 68918635(2S,4R)-1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-amine

Product 1

HCID 57595499(2S,4R)-4-Chloro-N-ethyl-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-benzamideYield 25.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(2S,4R)-4-Chloro-N-ethyl-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-benzamide was synthesized as described in general procedure C, except following benzyl carbamate removal the amine was modified in the following manner. To a solution of (2S,4R)-(4-amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(4-methoxy-phenyl)-methanone (200 mg, 0.68 mmol) in 20 ml dichloromethane was added acetaldehyde (0.042 mL, 0.75 mmol). The reaction mixture was stirred 30 min at room temperature. Then sodium triacetoxyborohydride (0.156 g, 0.75 mmol) was added and the resulting reaction mixture was stirred at room temperature for 6 hours. N,N-diisopropylethylamine (0.3 mL, 2.3 mmol) and 4-chlorobenzoyl chloride (0.4 mL, 3.1 mmol) was added and stirred at room temperature overnight. Dichloromethane (40 ml) was added. The mixture was washed with 30 ml sodium hydroxide (1N). The organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with ethyl acetate-dichloromethane (1:4) to give 80 mg (24%) title compound

Workup

  1. custom(2S,4R)-4-Chloro-N-ethyl-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-benzamide was synthesized
  2. custombenzyl carbamate removal the amine
  3. customthe resulting reaction mixture
  4. stirringwas stirred at room temperature for 6 hours
  5. stirringstirred at room temperature overnight
  6. washThe mixture was washed with 30 ml sodium hydroxide (1N)
  7. dry with materialThe organic layer was dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with ethyl acetate-dichloromethane (1:4)

Sources & evidence

ORD record
ord-2d590b77661e4103beba86070db7f71d
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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