4-chloro-N-ethylaniline → HCID 58732800, compound

HRID 553015Notes

Reaction equation

HRID 553015 reaction equation
[CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1)[CH3:2].C[Al](C)C.CO[C:17]([C@H:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]([C:29]([C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)=[O:30])[C@@H:21]([CH3:37])[CH2:20]1)=[O:18]>C1(C)C=CC=CC=1>[Cl:10][C:7]1[CH:8]=[CH:9][C:4]([N:3]([CH2:1][CH3:2])[C:17]([C@@H:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]([C:29]([C:31]3[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=3)=[O:30])[C@@H:21]([CH3:37])[CH2:20]2)=[O:18])=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 5878414-chloro-N-ethylanilineHCID 16682925TrimethylaluminumHCID 67166675HCID 67166675, compound

Product 1

HCID 58732800HCID 58732800, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of N-ethyl-4-chloroaniline (650 mg, 4.18 mmol) in anhydrous toluene at 10° C. was slowly added a 2M solution of trimethylaluminium in hexanes (2.1 mL, 4.18 mmol). The reaction mixture was stirred at room temperature until gas evolution stopped. A second round bottom flask was charged with cis-2-methyl-1-(pyridine-4-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid methyl ester (370 mg, 1.19 mmol) and the preformed aluminum amide was added. The resulting reaction mixture was refluxed for 20 hours. The reaction was concentrated, quenched with 1M aqueous hydrochloric acid at 0° C. (exothermic!), basified with 1M aqueous sodium hydroxide, and extracted with ethyl acetate. The resulting organic layer was separated, washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford an orange oil which was purified via flash chromatography (1% methanol/methylene chloride) followed by HPLC to provide (±)-trans-2-methyl-1-(pyridine-4-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (11%). 1H-NMR (CDCl3) δ: 1.02-1.18 (m, 6H), 1.60-1.70 (m, 1H), 2.45-2.55 (m, 1H), 3.60-3.70 (m, 1H), 3.80 (q, 2H), 4.98-5.10 (m, 1H), 6.40 (d, 1H), 6.90 (m, 2H), 7.00 (t, 1H), 7.30 (m, 2H), 7.50 (d, 2H), 7.60 (d, 2H), 8.55 (d, 2H). MS m/z: 434/436 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas refluxed for 20 hours
  3. concentrationThe reaction was concentrated
  4. customquenched with 1M aqueous hydrochloric acid at 0° C. (exothermic!)
  5. extractionextracted with ethyl acetate
  6. customThe resulting organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customto afford an orange oil which
  12. customwas purified via flash chromatography (1% methanol/methylene chloride)

Sources & evidence

ORD record
ord-3a28aa527da34849bc5286c2967c821a
Source dataset
uspto-grants-2011_05
Patent number
US07951950B2

Reaction notes

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