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

HRID 2278422Notes

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:22]=[CH:21][N:20]=[C:19]([N:23]2[CH2:28][C@H:27]([CH3:29])[O:26][C@H:25]([CH3:30])[CH2:24]2)[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:19]2[CH:18]=[C:17]([C:9]3[CH:13]=[CH:12][O:11][C:10]=3[CH3:14])[CH:22]=[CH:21][N:20]=2)[CH2:24]1

Participants

Conditions

Temperature: 100 °C

Procedure

4,4,5,5-Tetramethyl-2-(2-methyl-3-furanyl)-1,3,2-dioxaborolane (0.918 g, 4.41 mmol) was added to a solution of cis-4-(4-chloro-2-pyridinyl)-2,6-dimethylmorpholine (1 g, 4.41 mmol) in a mixture of 1,4-dioxane (17 mL), water (2.83 mL) and sodium carbonate (0.935 g, 8.82 mmol). The solution was degassed using argon gas and then charged with tetrakis(triphenylphosphine)palladium(0) (0.510 g, 0.441 mmol). After addition, the reaction mixture was stirred and heated in the microwave at 100° C. for 4 hours. 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 (˜10 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 (336 mg, 1.172 mmol, 26.6% yield). LC/MS [M+H]+=273.

Workup

customThe solution was degassed
additionAfter addition

Sources & evidence

ORD record: ord-4688c78171494b88b3dbf26e34d26641
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133178B2

Reaction notes

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