Dimethylformamide → HCID 67740281, compound

HRID 580954Notes

Reaction equation

HRID 580954 reaction equation
[CH2:1]([C:4]1[CH:16]=[C:15](Br)[CH:14]=[CH:13][C:5]=1[O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:2]=[CH2:3].[C:18]([C:20]1([OH:28])[CH:25]2[CH2:26][CH2:27][N:22]([CH2:23][CH2:24]2)[CH2:21]1)#[CH:19].C(N(CC)CC)C.CN(C)C=O>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.O>[CH2:1]([C:4]1[CH:16]=[C:15]([C:19]#[C:18][C:20]2([OH:28])[CH:25]3[CH2:26][CH2:27][N:22]([CH2:23][CH2:24]3)[CH2:21]2)[CH:14]=[CH:13][C:5]=1[O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:2]=[CH2:3]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 54094066HCID 54094066, compound

Product 1

HCID 67740281HCID 67740281, compoundYield 19.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 2-allyl-4-bromophenoxyacetate (912 mg), 3-ethynyl-3-hydroxyquinuclidine (453 mg), bis (triphenylphosphine)-palladium (II) chloride (106 mg), copper (I) iodide (53 mg), triethylamine (3 ml) and dimethylformamide (6 ml) was stirred at 80° C. under an atmosphere of argon for 8 hours. The reaction mixture was cooled to ambient temperature and water (100 ml) was added. The mixture was extracted with ethyl acetate (3×50 ml). The ethyl acetate extracts were combined and filtered. The filtrate was washed with saturated brine solution (3×50 ml), dried (MgSO4) and evaporated. The residue was purified by column chromatography on Alumina (Fluka 507C) using ethyl acetate containing 2.5% methanol as eluent to give 3-[2-(3-allyl-4-ethoxycarbonylmethyloxyphenyl)ethynyl]quinuclidin-3-ol (220 mg) as a solid, mp 95.9° C.; microanalysis, found: C, 70.7; H, 7.30; N, 3.50%; C22H27NO4.0.25 H2O requires: C, 70.6; H, 7.35; H, 3.72%; NMR (CDCl3): 1.28 (3H, t), 1.34-1.47 (1H, m), 1.52-1.72 (1H, m), 1.90-2.25 (3H, m), 2.25-2.60 (1H, m), 2.62-2.92 (4H, m), 2.97-3.09 (IH, d), 3.25-3.35 (1H, d of d), 3.42 (2H, d), 4.26 (2H, q), 4.62 (2H, s), 5.02-5.15 (2H, m), 5.88-6.08 (1H, m), 6.60-6.68 (1H, m) and 7.17-7.27 (2H, m); m/z 370 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×50 ml)
  3. filtrationfiltered
  4. washThe filtrate was washed with saturated brine solution (3×50 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was purified by column chromatography on Alumina (Fluka 507C)

Sources & evidence

ORD record
ord-002c755b5e124dbdb546638f8ef80d1c
Source dataset
uspto-grants-1999_07
Patent number
US05919793

Reaction notes

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