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

HRID 2183506ノート

反応式

HRID 2183506 の反応式
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]

参加物

9

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
70 °C

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-779157ba6aca48b8b3e75eea7d7a20dd
出典データセット
uspto-grants-2005_05
特許番号
US06900209B2

反応ノート

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