Pyridine → tert-Butyl (6-(chloromethyl)pyridin-2-yl)carbamate

HRID 520856ノート

反応式

HRID 520856 の反応式
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14]O)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.O=S(Cl)[Cl:25]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][Cl:25])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 19349090Tert-butyl (6-(hydroxymethyl)pyridin-2-yl)carbamate

生成物 1

HCID 21851761tert-Butyl (6-(chloromethyl)pyridin-2-yl)carbamate収率 50%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of ethyl 6-[(tert-butoxycarbonyl)amino]pyridine-2-carboxylate (456 mg, 1.71 mmol) in anhydrous ethanol (20 ml) was added pulverized CaCl2 (395 mg, 3.42 mmol). The suspension was stirred and cooled to 0° C. and NaBH4 (325 mg, 8.55 mmol) was added slowly. The reaction was stirred at 0° C. for 2 h, quenched with water, and extracted with CHCl3 (×3). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (30→50% ethyl acetate in hexane) to yield a colorless syrup (308 mg) as a mixture containing tert-butyl[6-(hydroxymethyl)pyridin-2-yl]carbamate as the major component (˜4:1 ratio). To a solution of the above mixture in CH2Cl2 (10 ml) was added pyridine (144 μl, 1.79 mmol) and SOCl2 (120 μl, 1.65 mmol). The reaction was stirred at room temperature for 4 h, quenched with water and saturated Na2CO3, and extracted with CHCl3. The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to yield the title compound as a colorless syrup (208 mg, 50% over 2 steps).

後処理

  1. customquenched with water and saturated Na2CO3
  2. extractionextracted with CHCl3
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel (10% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-9bacc23f54274ff09f4f36e9f5754456
出典データセット
uspto-grants-2016_05
特許番号
US09328067B2

反応ノート

読み込み中…