Dimethylformamide → 3-[2-(4-{2-Methoxyethoxy}-3,5-dimethylphenyl)ethynyl]quinuclidin-3-ol

HRID 580959Notes

Reaction equation

HRID 580959 reaction equation
Br[C:2]1[CH:12]=[C:11]([CH3:13])[C:5]([O:6][CH2:7][CH2:8][O:9][CH3:10])=[C:4]([CH3:14])[CH:3]=1.[CH3:15][N:16]([CH3:19])[CH:17]=O>C(N(CC)CC)C.[OH-].[Na+].[Cu]I>[CH3:10][O:9][CH2:8][CH2:7][O:6][C:5]1[C:11]([CH3:13])=[CH:12][C:2]([C:3]#[C:4][C:5]2([OH:6])[CH:11]3[CH2:13][CH2:19][N:16]([CH2:17][CH2:12]3)[CH2:15]2)=[CH:3][C:4]=1[CH3:14]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 541527811-(4-Bromo-2,6-dimethylphenoxy)-2-methoxyethane

Product 1

HCID 678504423-[2-(4-{2-Methoxyethoxy}-3,5-dimethylphenyl)ethynyl]quinuclidin-3-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8471TriethylamineSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
65 °C

Procedure

1-(4-bromo-2,6-dimethylphenoxy)-2-methoxyethane (704 mg) and copper (I) iodide (48 mg) in dimethylformamide (DMF) (5.5 ml) and triethylamine (2.7 ml) at ambient temperature and under an atmosphere of argon. The mixture was heated at 65° C. for 14 hours, cooled to ambient temperature, diluted with 2M aqueous sodium hydroxide (20 ml) and extracted with diethyl ether (5×100 ml). The ethereal extracts were combined, washed with water (100 ml) and saturated brine (100 ml), dried (K2CO3) and evaporated. The residue was crystallised from acetonitrile to give 3-[2-(4-{2-methoxyethoxy}-3,5-dimethylphenyl)ethynyl]quinuclidin-3-ol (130 mg) as a solid, m.p. 120° C.; microanaylsis, found: C, 72.4; H, 8.2; N, 4.1%; C2OH27NO3 requires: C, 72.9; H, 8.3; N, 4.2%; NMR([CD3)2SO): 1.3(1H,m), 1.57(1H,m), 1.9(3H,m), 2.21(6H,s), 2.65(4H,m), 2.8(1H,d), 3.02(1H,d), 3.31(3H,s), 3.61(2H,m), 3.87(2H,m), 5.5(1H,br) and 7.07(2H,s); m/z 330 (M+H).

Workup

  1. customat ambient temperature
  2. temperaturecooled to ambient temperature
  3. extractionextracted with diethyl ether (5×100 ml)
  4. washwashed with water (100 ml) and saturated brine (100 ml)
  5. dry with materialdried (K2CO3)
  6. customevaporated
  7. customThe residue was crystallised from acetonitrile

Sources & evidence

ORD record
ord-fbe52ca1885e4747bfdcb31e83805588
Source dataset
uspto-grants-1999_07
Patent number
US05919793

Reaction notes

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