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

HRID 1424286Notes

Reaction equation

HRID 1424286 reaction equation
[CH3:1][CH:2]([CH3:19])[CH2:3][C:4]([C:6]1[CH:18]=[CH:17][C:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:8][CH:7]=1)=O.[CH3:20][C:21]1[CH:22]=[N+:23]([O-])[C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2.C([N:35](C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>ClCCl.C(=O)(O)[O-].[Na+]>[CH3:1][CH:2]([CH3:19])[CH2:3][CH:4]([C:6]1[CH:18]=[CH:17][C:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:8][CH:7]=1)[NH:35][C:22]1[C:21]([CH3:20])=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 70214663-Methylquinoline N-oxideHCID 71239698Tert-butyl 4-(3-methylbutanoyl)benzoate

Product 1

HCID 71243814Tert-butyl (+/-)-4-(3-methyl-1-((3-methylquinolin-2-yl)amino)butyl)benzoate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of tert-butyl(+/−)-4-(3-methylbutanoyl)benzoate (527 mg, 2.00 mmol) and 3-methylquinoline N-oxide (318 mg, 2.00 mmol) in dichloromethane (8.0 mL) was added diisopropylethylamine (1.31 mL, 7.50 mmol) followed by bromotripyrrolidinophosphonium hexafluorophosphate (1.18 g, 2.50 mmol). The solution was stirred at room temperature for 18 hours then diluted with sat. aq sodium bicarbonate (20 mL). The mixture was extracted with ethyl acetate (3×20 mL). The combined organics were dried over anhydrous Na2SO4 and filtered, and the filtrate was concentrated. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave tert-butyl(+/−)-4-(3-methyl-1-((3-methylquinolin-2-yl)amino)butyl)benzoate as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J=8.2 Hz, 2H), 7.63 (d, J=8.2 Hz, 1H), 7.59 (s, 1H), 7.54-7.48 (m, 3H), 7.47-7.41 (m, 1H), 7.19-7.13 (m, 1H), 5.56 (q, J=7.4 Hz, 1H), 4.73 (d, J=7.0 Hz, 1H), 2.28 (s, 3H), 1.94-1.83 (m, 1H), 1.81-1.70 (m, 1H), 1.70-1.60 (m, 1H), 1.57 (s, 9H), 1.04 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  2. dry with materialThe combined organics were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-5e421d8a984e4b71876a24b41ffc34f5
Source dataset
uspto-grants-2015_01
Patent number
US08927577B2

Reaction notes

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