Water → cis-2,6-Dimethyl-4-[6-(2-methyl-3-furanyl)-2-pyridinyl]morpholine

HRID 2278425Notes

Reaction equation

HRID 2278425 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:13]=[CH:12][O:11][C:10]=2[CH3:14])O1.Br[C:17]1[N:22]=[C:21]([N:23]2[CH2:28][C@H:27]([CH3:29])[O:26][C@H:25]([CH3:30])[CH2:24]2)[CH:20]=[CH:19][CH:18]=1.O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:30][C@H:25]1[O:26][C@@H:27]([CH3:29])[CH2:28][N:23]([C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([C:9]3[CH:13]=[CH:12][O:11][C:10]=3[CH3:14])[N:22]=2)[CH2:24]1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium Carbonate2×HCID 242295474,4,5,5-Tetramethyl-2-(2-methylfuran-3-yl)-1,3,2-dioxaborolane2×HCID 86702423cis-4-(6-Bromo-2-pyridinyl)-2,6-dimethylmorpholine

Product 1

HCID 67514523cis-2,6-Dimethyl-4-[6-(2-methyl-3-furanyl)-2-pyridinyl]morpholine

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4,4,5,5-Tetramethyl-2-(2-methyl-3-furanyl)-1,3,2-dioxaborolane (412 mg, 1.980 mmol) was added to a solution of cis-4-(6-bromo-2-pyridinyl)-2,6-dimethylmorpholine (537 mg, 1.980 mmol) in a mixture of 1,4-dioxane (15 mL), water (2.500 mL) and sodium carbonate (420 mg, 3.96 mmol). The solution was degassed using argon gas and then charged with tetrakis(triphenylphosphine)palladium(0) (229 mg, 0.198 mmol). After addition, the reaction mixture was stirred and heated in the microwave at 100° C. for 1 hour. Crude LC/MS showed starting material and desired product so tetrakis(triphenylphosphine) palladium(0) (229 mg, 0.198 mmol), sodium carbonate (420 mg, 3.96 mmol) and 4,4,5,5-tetramethyl-2-(2-methyl-3-furanyl)-1,3,2-dioxaborolane (412 mg, 1.980 mmol) were added to the reaction mixture which was then stirred and heated at 100° C. in the microwave for 1 hour. Crude LC/MS showed desired product and no starting material can be seen. The reaction mixture was washed with ethyl acetate (200 mL), water (100 mL), filtered and then evaporated to dryness. The residue was dissolved in dichloromethane (˜5 ml) and purified on silica by a Biotage SP4 chromatographic system (40+M cartridge, eluted with 0-50% ethyl acetate in isohexanes). Fractions containing pure product were combined and concentrated under reduced pressure to give the title compound as a colourless oil (270 mg, 0.942 mmol, 47.6% yield). LC/MS [M+H]+=273.

Workup

  1. customThe solution was degassed
  2. additionAfter addition

Sources & evidence

ORD record
ord-6a1da768e85f4698848cdf14eb43ef0e
Source dataset
uspto-grants-2015_09
Patent number
US09133178B2

Reaction notes

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