Ammonium Chloride → 1-Tert-butyl 3-methyl 3-(5-chloropyridin-2-yl)azetidine-1,3-dicarboxylate

HRID 69527ノート

反応式

HRID 69527 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5](F)=[N:6][CH:7]=1.[N:9]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][CH:11]([C:13]([O:15][CH3:16])=[O:14])[CH2:10]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[NH4+].[Cl-]>C1(C)C=CC=CC=1>[CH3:16][O:15][C:13]([C:11]1([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:12][N:9]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:10]1)=[O:14]

参加物

6

反応物 4

HCID 25517Ammonium ChlorideHCID 3458175-Chloro-2-fluoropyridineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 446076271-tert-Butyl 3-methyl azetidine-1,3-dicarboxylate

生成物 1

HCID 866919031-Tert-butyl 3-methyl 3-(5-chloropyridin-2-yl)azetidine-1,3-dicarboxylate

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of 5-chloro-2-fluoropyridine (0.5 g, 3.8 mmol, Eq: 1.00) and 1-tert-butyl 3-methyl azetidine-1,3-dicarboxylate (818 mg, 3.8 mmol, Eq: 1.00) in toluene (5 ml) was added dropwise at 0° C. for 15 min a 0.5 M solution of KHMDS (7.6 ml, 3.8 mmol, Eq: 1.00) in toluene. The colorless solution turned into yellow-orange. After stirring at 0° C. for 45 min, the reaction mixture was allowed to warm to 20° C. and stirred for 2.5 h. A saturated aqueous NH4Cl solution (50 ml) was added and the aqueous phase was extracted with AcOEt (2×75 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, 12 g, 10% to 60% AcOEt in heptane) to yield a colorless gum (0.234 g; 19%). m/z=327.2 [M+H]+.

後処理

  1. temperatureto warm to 20° C.
  2. stirringstirred for 2.5 h
  3. extractionthe aqueous phase was extracted with AcOEt (2×75 ml)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by flash chromatography (silica gel, 12 g, 10% to 60% AcOEt in heptane)
  9. customto yield a colorless gum (0.234 g; 19%)

出典と根拠

ORDレコード
ord-145d6c843df14c13afb62e1ae7984d5d
出典データセット
uspto-grants-2014_09
特許番号
US08822505B2

反応ノート

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