Pyridine → HCID 11020867, compound

HRID 840413Notes

Reaction equation

HRID 840413 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:13]([O:15][CH3:16])=[O:14])[C:5]2[C:10]([C:11]=1Br)=[CH:9][CH:8]=[CH:7][CH:6]=2.[Cu][C:18]#[N:19].[N:20]1C=CC=C[CH:21]=1.CN1CCCC1=O>O.[NH4+].[OH-].CCOC(C)=O>[C:21]([C:2]1[CH:3]=[C:4]([C:13]([O:15][CH3:16])=[O:14])[C:5]2[C:10]([C:11]=1[C:18]#[N:19])=[CH:9][CH:8]=[CH:7][CH:6]=2)#[N:20]

Participants

8

Reactant 4

HCID 1049PyridineHCID 13387N-methyl-2-pyrrolidoneHCID 11089197HCID 11089197, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 11020867HCID 11020867, compoundYield 26.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture containing methyl 3,4-dibromo-1-naphthoate (126 mg, 0.366 mmol), copper (I) cyanide (618 mg, 6.89 mmol), pyridine (0.1 mL), and dry N-methylpyrrolidinone (2.0 mL) was heated at approximately 150° C. for 1 h. cooled to room temperature, diluted with water, NH4OH and EtOAc. The mixture was stirred briefly and filtered. The organic phase was separated and the aqueous phase extracted with additional EtOAc. The combined organic extracts were washed (dilute aqueous NH4OH and saturated NaHCO3). dried (Na2SO4), filtered, and EtOAc was removed in vacuo. The products were separated by chromatography (5-15% EtOAc in hexane and hexane:DCM (2:1)) to afford methyl 3,4-dicyano-1-naphthoate (22 mg; 25%) [1H NMR (CDCl3) δ 9.01 (m, 1H), 8.41 (m, 1H), 8.36 (s, 1H), 7.9 (m, 2H), 4.08 (s, 3H); MS (EI) m/z 236 (M)], methyl 3-bromo-4-cyano-1-naphthoate (21.9 mg; 20.6%) [1H NMR (CDCl3) δ 8.86 (m, 1H), 8.31 (s, 1H), 8.28 (m, 1H). 7.75 (m, 2H), 4.05 (s, 3H); MS (EI) m/z 289 (M).], and methyl 4-bromo-3-cyano-1-naphthoate (28.3 mg; 26.6%) [1H NMR (CDCl3) δ 9.02 (m, 1H), 8.43 (m, 1H), 8.28 (s, 1H), 7.8 (m, 2H) 4.04 (s, 3H); MS (EI) m/z 289 (M)]. The esters were separately saponified by stirring with 1.1-1.2 equivalents of LiOH in THF:water:methanol (20:10:1) at room temperature. The solutions were concentrated in vacuo, diluted with additional water, acidified with 1N HCl, extracted with EtOAc, dried (Na2SO4), filtered, and the EtOAc was removed in vacuo to afford the individual carboxylic acids. Prior to use, the 3,4-dicyano-1-naphthoic acid was further purified by chromatography (10-20% methanol in DCM) to afford the title compound (15.3 mg, 87%) as an off-white solid. MS (EI) m/z 222 (M).

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered
  3. customThe organic phase was separated
  4. extractionthe aqueous phase extracted with additional EtOAc
  5. washThe combined organic extracts were washed (dilute aqueous NH4OH and saturated NaHCO3)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customEtOAc was removed in vacuo
  9. customThe products were separated by chromatography (5-15% EtOAc in hexane and hexane:DCM (2:1))

Sources & evidence

ORD record
ord-b0a21ef534494852ab2d97509ab72a02
Source dataset
uspto-grants-2002_04
Patent number
US06365602B1

Reaction notes

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