Diisopropylamine → 1-(Pyridin-2-yl)-2-(quinolin-4-yl)ethanone

HRID 902011Notes

Reaction equation

HRID 902011 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[N:19]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:22]([CH3:23])=[CH:21][CH:20]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36](OCC)=[O:37]>C1COCC1>[N:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36](=[O:37])[CH2:23][C:22]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:19]=[CH:20][CH:21]=1

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 8058HexaneHCID 102854-MethylquinolineHCID 17307Ethyl 2-pyridinecarboxylateHCID 178418339Butyllithium

Product 1

HCID 109338561-(Pyridin-2-yl)-2-(quinolin-4-yl)ethanoneYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (44.9 mL, 320 mmol) in THF (500 mL) at −78° C. add 1.6 M n-butyl lithium in hexane (200 mL, 320 mmol). Stir for 10 minutes and add dropwise a solution of lepidine (42.9 g, 300 mmol) in THF (200 mL) over 20 minutes at −78° C. and quickly add a solution of ethyl picolinate (48.3 g, 320 mmol). Allow the reaction to warm slowly to 0° C. and quench by pouring into water (1 L). Add ethyl acetate (1 L). Dissolve residual solids by adding Acetic acid (20 mL). Separate the layers and extract the aqueous layer with one portion of ethyl acetate (100 mL). Combine the organic extracts, dry over sodium sulfate, and concentrate in vacuo. Triturate the crude oil with hexane/ether to give 36 g of the title compound. Concentrate the filtrate. Chromatograph the residue on silica gel (elute with 10:9:1 CH2Cl2, ether, MeOH). Precipitate the purified product from ether/hexane to give 21 g of the title compound. Combined yield: 57 g (76%) of title compound as a yellow crystalline solid. MS ES+ m/e 249.0 (M+1).

Workup

  1. customthe reaction
  2. customquench
  3. additionby pouring into water (1 L)
  4. dissolutionDissolve residual solids
  5. additionby adding Acetic acid (20 mL)
  6. customSeparate the layers
  7. extractionextract the aqueous layer with one portion of ethyl acetate (100 mL)
  8. dry with materialCombine the organic extracts, dry over sodium sulfate
  9. concentrationconcentrate in vacuo
  10. customTriturate the crude oil with hexane/ether

Sources & evidence

ORD record
ord-7a23bb77d33641979964b223fc55a312
Source dataset
uspto-grants-2008_04
Patent number
US07365066B2

Reaction notes

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