Dimethylformamide → (5)-1-(Cyclopropanecarbonyl)-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinoline-6-carbonitrile

HRID 1051718Notes

Reaction equation

HRID 1051718 reaction equation
Br[C:2]1[C:3]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])[C@@H:7]([CH3:17])[CH2:6][CH2:5]2.C(OCC)(=O)C.[CH3:31][N:32](C)C=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[CH:14]1([C:12]([N:8]2[C:9]3[C:4](=[C:3]([O:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:2]([C:31]#[N:32])=[CH:11][CH:10]=3)[CH2:5][CH2:6][C@@H:7]2[CH3:17])=[O:13])[CH2:16][CH2:15]1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 118086215(S)-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone

Product 1

HCID 118076090(5)-1-(Cyclopropanecarbonyl)-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinoline-6-carbonitrileYield 32%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
160 °C

Procedure

A mixture of (S)-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.100 g, 0.26 mmol), tetrakis(triphenylphosphine)palladium (O) (0.30 g, 0.03 mmol), and zinc cyanide (0.036 g, 0.31 mmol) in N,N-dimethylformamide (2 mL) was heated with microwave irradiation for 30 min at 160° C. The reaction mixture was cooled to room temperature, poured into ethyl acetate (10 mL), washed with water (3×2 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1:8, ethyl acetate/petroleum ether) to afford (5)-1-(cyclopropanecarbonyl)-2-methyl-5-phenoxy-1,2,3,4-tetrahydroquinoline-6-carbonitrile (0.27 g, 32%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ ppm 0.74-0.82 (m, 1H), 0.90-1.10 (m, 2H), 1.10-1.18 (m, 3H), 1.28-1.39 (m, 1H), 1.49-1.61 (m, 1H), 1.80-1.91 (m, 1H), 2.10-2.22 (m, 1H), 2.39-2.51 (m, 1H), 2.67-2.80 (m, 1H), 4.71-4.89 (m, 1H), 6.85 (d, J=8.10 Hz, 2H), 7.08 (t, J=7.50 Hz, 1H), 7.28-7.38 (m, 2H), 7.40-7.47 (m, 1H), 7.49-7.55 (m, 1H). MS (ESI, pos. ion) m/z 333 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (3×2 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified via column chromatography on silica gel (eluting with 1:8, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-7789948d93a0499abe9cd811a7775ce7
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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