Sodium Bicarbonate → 1-(6-Chloro-3-pyridinyl)-4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-piperazine

HRID 79152

反応式

HRID 79152 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:9][C:10]([Si:13]([CH3:24])([CH3:23])[O:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([CH3:12])[CH3:11].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].C(=O)(O)[O-].[Na+]>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].C1(C)C=CC=CC=1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([N:20]2[CH2:19][CH2:18][N:17]([CH2:16][CH2:15][O:14][Si:13]([C:10]([CH3:12])([CH3:11])[CH3:9])([CH3:23])[CH3:24])[CH2:22][CH2:21]2)=[CH:3][CH:4]=1

参加物

8

反応物 5

HCID 516892Sodium BicarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27344145-Bromo-2-chloropyridineHCID 23676156Sodium t-butoxideHCID 582998241-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)piperazine

生成物 1

HCID 582997451-(6-Chloro-3-pyridinyl)-4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-piperazine収率 92.7%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

5-Bromo-2-chloropyridine (3.15 g, 16.4 mmol), compound 246 (4.00 g, 16.4 mmol), Pd2(dba)3 (0.749 g, 0.818 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.947 g, 1.64 mmol) and sodium tert-butoxide (1.82 g, 19.0 mmol) were combined in a screw cap vial and solvated under argon atmosphere with degassed toluene (44 mL). The reaction was briefly sparged with argon, then sealed and stirred at 100° C. After 3 h, the reaction contents were poured into saturated sodium bicarbonate (100 mL) and extracted with 10% methanol in dichloromethane (3×200 mL). The combined organics were dried with sodium sulfate and concentrated in vacuo. Silica gel chromatography (gradient elution 0 to 100% ethyl acetate in hexanes switching to 3% methanol in DCM) afforded compound 247 (5.40 g, 92.7% yield). 1H NMR (500 MHz, CDCl3) δ 0.08 (s, 6 H) 0.91 (s, 9 H) 2.60 (t, J=5.87 Hz, 2 H) 2.70 (br. s., 4 H) 3.20 (d, J=4.40 Hz, 4 H) 3.80 (t, J=6.11 Hz, 2 H) 7.17 (d, J=1.71 Hz, 2 H) 8.02 (s, 1 H) ppm.

後処理

  1. customcap vial
  2. customThe reaction was briefly sparged with argon
  3. customsealed
  4. customthe reaction contents
  5. extractionextracted with 10% methanol in dichloromethane (3×200 mL)
  6. dry with materialThe combined organics were dried with sodium sulfate
  7. concentrationconcentrated in vacuo
  8. washSilica gel chromatography (gradient elution 0 to 100% ethyl acetate in hexanes switching to 3% methanol in DCM)

出典と根拠

ORDレコード
ord-46bc2367015c41a9997e791895d18b5a
出典データセット
uspto-grants-2014_09
特許番号
US08841312B2

関連ノート

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