Dimethylformamide → HCID 22622309, compound

HRID 840411Notes

Reaction equation

HRID 840411 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:14]([O:16][CH2:17]C)=[O:15])[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2.[CH3:19][N:20](C=O)C>C(Cl)Cl.[C-]#N.[C-]#N.[Zn+2].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:19]([C:2]1[CH:3]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2)#[N:20]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 15094553HCID 15094553, compound

Product 1

HCID 22622309HCID 22622309, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl 3-bromo-6-methoxy-1-naphthoate (Wrobel, et al; J. Med. Chem. 34, 2504 (1991) (206 mg, 0.66 mmol), Zn(CN)2, and tetrakis(triphenylphosphine) palladium (36 mg, 0.031 mmol) in DMF (12 mL) was stirred at 80° C. for 1 h. The mixture was diluted with DCM, washed with water, dried (MgSO4), filtered and concentrated to a yellow precipitate, and purified by chromatography (5% EtOAc in hexanes) to afford methyl 3-cyano-6-methoxy-1-naphthoate as a white powder (150 mg, 0.588 mmol, 88%). The ester was saponified by stirring in 2% water in THF with 1.5 equivalents of LiOH at 80° C. for 3 h to afford the title compound. 1H NMR (CDCl3) δ 8.99 (d, J=9.6, 1H), 8.33 (s, 1H), 7.45 (dd, J=9.3, 2.7, 1H), 7.26 (s, 1H), 7.22 (d, J=2.4, 1H).

Workup

  1. washwashed with water
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to a yellow precipitate
  5. custompurified by chromatography (5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-bba5052334af4f719a0fb7b0f6ebbeff
Source dataset
uspto-grants-2002_04
Patent number
US06365602B1

Reaction notes

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