Diisopropylethylamine → Ethyl(+/-)-4-(1-((3-methylquinolin-2-yl)amino)butyl)benzoate

HRID 1424245Notes

Reaction equation

HRID 1424245 reaction equation
[NH2:1][CH:2]([C:6]1[CH:16]=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5].[CH3:17][C:18]1[CH:19]=[N+:20]([O-])[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>C([O-])(O)=O.[Na+].ClCCl>[CH3:17][C:18]1[C:19]([NH:1][CH:2]([C:6]2[CH:16]=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][CH:7]=2)[CH2:3][CH2:4][CH3:5])=[N:20][C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 70214663-Methylquinoline N-oxide2×HCID 71243833Ethyl(+/-)-4-(1-aminobutyl)benzoate

Product 1

HCID 71243834Ethyl(+/-)-4-(1-((3-methylquinolin-2-yl)amino)butyl)benzoate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Intermediate 2 (22.9 g, 104 mmol) was combined with 3-methylquinoline-N-oxide (Intermediate 3, 17.3 g, 109 mmol) and dichloromethane (414 mL). Diisopropylethylamine (68.0 mL, 389 mmol) was added, followed by bromotripyrrolidinophosphonium hexafluorophosphate (61.0 g, 130 mmol). The solution was stirred at room temperature for 12 h before diluting with sat. aq NaHCO3 (400 mL). The mixture was extracted with ethyl acetate (3×400 mL). The combined organics were dried over Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave ethyl(+/−)-4-(1-((3-methylquinolin-2-yl)amino)butyl)benzoate (Intermediate 4). 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J=8.2 Hz, 2H), 7.65-7.58 (m, 2H), 7.56-7.48 (m, 3H), 7.43 (t, J=7.5 Hz, 1H), 7.16 (t, J=7.4 Hz, 1H), 5.50 (q, J=7.2 Hz, 1H), 4.79 (d, J=7.0 Hz, 1H), 4.35 (q, J=7.0 Hz, 2H), 2.30 (s, 3H), 2.04-1.83 (m, 2H), 1.54-1.39 (m, 2H), 1.37 (t, J=7.1 Hz, 3H), 0.98 (t, J=7.4 Hz, 3H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×400 mL)
  2. dry with materialThe combined organics were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-07736b43226943d4bf1546a96189dbfa
Source dataset
uspto-grants-2015_01
Patent number
US08927577B2

Reaction notes

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