Nitrogen → 4-[6-(Tert-butyldimethylsilanyloxymethyl)-pyridin-2-yl]morpholine

HRID 2183506Notes

Reaction equation

HRID 2183506 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[N:3]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N#N.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOCC>[Si:10]([O:9][CH2:8][C:4]1[N:3]=[C:2]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:7]=[CH:6][CH:5]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

9

Reactant 5

HCID 947NitrogenHCID 8083MorpholineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 11483477Pyridine, 2-bromo-6-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-HCID 23676156Sodium t-butoxide

Product 1

HCID 224731974-[6-(Tert-butyldimethylsilanyloxymethyl)-pyridin-2-yl]morpholineYield 72.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 2-bromo-6-(tert-butyldimethylsilanyloxymethyl)pyridine (J. Org. Chem.; 1993; 4389-4397) (500 mg, 1.66 mmol), morpholine (173 μl, 2.0 mmol), 1,3-bis(diphenylphosphino)propane (68 mg, 10 mol %) in toluene (20 ml) was degassed with a stream of N2 for 15 min. Sodium tert-butoxide (222 mg, 2.31 mmol) and Pd2(dba)3 (76 mg, 5 mol %) were added and the reaction mixture was heated at 70° C. overnight under N2. After cooling to room temperature, Et2O (100 ml) was added and the solution was washed with brine (25 ml), dried and concentrated under reduced. The mixture was purified by column chromatography on silica using 30% Et2O/iso-hexanes as eluent to yield the desired aminopyridine (370 mg, 72%). 1H NMR (400 MHz, CDCl3) δ 7.40 (1H, dd, J=8.6, 7.4 Hz), 6.75 (1H, d, J=7.4 Hz), 6.38 (1H, d, J=8.6 Hz), 4.56 (2H, s), 3.70 (4H, t, J=5.0 Hz), 3.36 (4H, t, J=5.0 Hz), 0.84 (9H, s), 0.00 (6H, s). m/z (ES+) 309 (M+H+).

Workup

  1. temperatureAfter cooling to room temperature
  2. washthe solution was washed with brine (25 ml)
  3. customdried
  4. concentrationconcentrated
  5. customThe mixture was purified by column chromatography on silica using 30% Et2O/iso-hexanes as eluent

Sources & evidence

ORD record
ord-779157ba6aca48b8b3e75eea7d7a20dd
Source dataset
uspto-grants-2005_05
Patent number
US06900209B2

Reaction notes

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