1-Naphthalenecarbonitrile → HCID 14839227, compound

HRID 2165877Notes

Reaction equation

HRID 2165877 reaction equation
[CH2:1]([Li:5])[CH2:2][CH2:3][CH3:4].[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+].C[CH:15]([N-:17][CH:18](C)C)C.[C:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)#[N:22].[CH2:33]1[CH2:37][O:36][CH2:35][CH2:34]1>>[Li+:5].[CH3:7][CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])[CH3:8].[CH3:15][N:17]([CH3:18])[C:35]1[CH:34]=[C:33]2[C:3]([CH:4]=[C:21]([C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=[CH:25][CH:24]=3)[NH:22][C:37]2=[O:36])=[CH:2][CH:1]=1

Participants

7

Reactant 5

HCID 68461-NaphthalenecarbonitrileHCID 7912DiisopropylamineHCID 8028Tetrahydrofuran4×HCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 14839227HCID 14839227, compoundYield 24%

Procedure

Part D. A solution of LDA in THF was prepared by the dropwise addition of 1.6M n-butyllithium in hexanes (17 mL, 27 mmol) to a solution of diisopropylamine (4.0 mL, 28.5 mmol) in THF (50 mL) at -78°. A solution of the product of Part C (5.00 g, 24.2 mmol) in THF (15 mL) was added dropwise to the LDA solution at -78° and the reaction mixture was stirred for one hour at -78°. A solution of 1-cyanonaphthalene (3.70 g, 24.2 mmol) in THF (15 mL) was added dropwise to the reaction mixture at -78°, and the reaction mixture was stirred at -78° for 1 hour after complete addition and then allowed to gradually warm with stirring to room temperature for 2 hours. The reaction mixture was quenched with excess saturated aqueous NH4Cl. The layers were separated and the aqueous phase was extracted with ether. The combined organic extracts were washed with saturated NaCl, dried, and concentrated. The residue was recrystallized from ethyl acetate to afford 7-(dimethylamino)-3-(1-naphthalenyl)-1(2H)-isoquinolinone (1.84 g, 5.85 mmol, 24% yield) as a solid. The mother liquor was concentrated and the residue was recrystallized from 6:4:0.5 hexane-ethyl acetate-methanol to afford a second crop (1.41 g, 4.48 mmol, 19% yield) as a solid: mp 205°-206°; IR(CHCl3) 1650 cm-1 ; HRMS m/e calcd for C21H18N 2 O (M+) 314.1419, found 314.1426; 1H NMR(CDCl3) δ 8.72(s,1H), 8.00-8.17(m,1H), 7.83-8.00(m,2H), 7.38-7.70(m,6H), 7.10-7.29(m,1H), 6.63(s,1H), 3.10(s,6H). Anal. Calcd for C21H18N2O: C,80.23, H,5.77; N,8.91. Found: C,79.88; H,5.58; N,8.71.

Workup

  1. stirringthe reaction mixture was stirred at -78° for 1 hour
  2. additionafter complete addition
  3. temperatureto gradually warm
  4. stirringwith stirring to room temperature for 2 hours
  5. customThe reaction mixture was quenched with excess saturated aqueous NH4Cl
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with ether
  8. washThe combined organic extracts were washed with saturated NaCl
  9. customdried
  10. concentrationconcentrated
  11. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-07322aea0eba47df8e371ed82d66855b
Source dataset
uspto-grants-1990_07
Patent number
US04942163

Reaction notes

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