Morpholine → HCID 57421817, compound

HRID 1431709Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:12]1[CH2:13][CH2:14][N:9]([C:2]2[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=2)[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 5-chloro-3-hydroxypyridine (0.2 g, 1.6 mmol), morpholine (0.7 mL, 8.0 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-triisopropyl-biphenyl, (X-Phos) (0.12 g, 0.26 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.06 g, 0.07 mmol) in dry THF (2.0 mL) was degassed by nitrogen. To this mixture was added 1.0M lithium bis(trimethylsilyl)amide in THF (8.8 mL, 8.8 mmol) dropwise, and the resulting reaction was heated to 60° C. After 20.5 h, the reaction was cooled to rt then concd. The residue was purified on silica gel (0-100% of a premixed solution of 89:9:1 DCM:methanol:ammonium hydroxide in DCM) to afford an off white solid as 5-morpholinopyridin-3-ol. 1H NMR (500 MHz, DMSO-d6) δ ppm 9.62 (1H, br. s.), 7.79 (1H, d, J=2.4 Hz), 7.61 (1H, d, J=2.2 Hz), 6.65 (1H, t, J=2.4 Hz), 3.79 (4H, m), 3.16 (4H, m). Mass Spectrum (pos.) m/e: 181.0 (M+H)+.

Workup

customwas degassed by nitrogen
customthe resulting reaction
temperaturethe reaction was cooled to rt
customThe residue was purified on silica gel (0-100% of a premixed solution of 89:9:1 DCM:methanol:ammonium hydroxide in DCM)

Sources & evidence

ORD record: ord-d48ea56a4d6e4def8017ebc288bdfd0e
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

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