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

HRID 2278428Notes

Reaction equation

HRID 2278428 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:13]=[CH:12][O:11][C:10]=2[CH3:14])O1.Cl[C:17]1[CH:18]=[C:19]([N:23]2[CH2:28][C@H:27]([CH3:29])[O:26][C@H:25]([CH3:30])[CH2:24]2)[CH:20]=[CH:21][CH:22]=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>[CH3:29][C@H:27]1[O:26][C@@H:25]([CH3:30])[CH2:24][N:23]([C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([C:9]3[CH:13]=[CH:12][O:11][C:10]=3[CH3:14])[CH:18]=2)[CH2:28]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 242295474,4,5,5-Tetramethyl-2-(2-methylfuran-3-yl)-1,3,2-dioxaborolaneHCID 68056117cis-4-(3-Chlorophenyl)-2,6-dimethylmorpholine

Product 1

HCID 67513891cis-2,6-Dimethyl-4-[3-(2-methyl-3-furanyl)phenyl]morpholine

Reagents, catalysts & solvents 2

HCID 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 (1.645 g, 7.91 mmol) was added to a solution of cis-4-(3-chlorophenyl)-2,6-dimethylmorpholine (1.785 g, 7.91 mmol) in a mixture of 1,4-dioxane (17 mL), water (2.83 mL) and sodium carbonate (1.676 g, 15.82 mmol). The solution was degassed using argon gas and then charged with tetrakis(triphenylphosphine)palladium(0) (0.914 g, 0.791 mmol). After addition, the reaction mixture was stirred and heated in the microwave at 100° C. for 48 hours. Crude LC/MS showed desired product and only 26% of 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 (˜10 ml) and purified on silica by using a Biotage SP4 chromatographic system (65i 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 (0.74 g, 2.59 mmol, 32.8% yield). LC/MS [M+H]+=272.

Workup

  1. customThe solution was degassed
  2. additionAfter addition

Sources & evidence

ORD record
ord-8db1cf365d4d4f96850598fdc8232723
Source dataset
uspto-grants-2015_09
Patent number
US09133178B2

Reaction notes

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