Diisobutylaluminum hydride → tert-Butyl (4-(2-hydroxyethyl)pyridin-2-yl)carbamate

HRID 1774361ノート

反応式

HRID 1774361 の反応式
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[C:13]([CH2:15][C:16](OCC)=[O:17])[CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C>C1COCC1>[OH:17][CH2:16][CH2:15][C:13]1[CH:12]=[CH:11][N:10]=[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH:14]=1

参加物

4

反応物 2

HCID 14487Diisobutylaluminum hydride2 回HCID 53419364(2-Boc-amino-pyridin-4-yl)-acetic acid ethyl ester

生成物 1

HCID 58416767tert-Butyl (4-(2-hydroxyethyl)pyridin-2-yl)carbamate収率 70.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-69 °C

実験手順

To a solution of ethyl 2-(2-(tert-butoxycarbonylamino)pyridin-4-yl)acetate (WO 2007089512) (10.0 g, 35.7 mmol) under N2 in THF (100 mL), at −78° C., was added a solution of DIBAL in THF (1.0M, 71.0 mL, 71.0 mmol) over 1 hr. The reaction mixture was stirred at −78 to −60° C. for 40 min and was then warmed to −15° C. over 1 hr. The solution was re-cooled to −78° C. and was treated with a further aliquot of DIBAL solution (36.0 mL, 36.0 mmol) and was allowed to warm to −40° C. and stirred for 1 hr. The reaction was quenched by the cautious addition of water (10 mL), followed MgSO4. The solids were removed by filtration and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 330 g, EtOAc in hexanes, 65% v/v, isocratic elution) to give tert-butyl 4-(2-hydroxyethyl)pyridin-2-ylcarbamate, (6.0 g, 64%) as a yellow solid: m/z 239 (M+H)+ (ES+).

後処理

  1. temperaturewas then warmed to −15° C. over 1 hr
  2. temperatureThe solution was re-cooled to −78° C.
  3. temperatureto warm to −40° C.
  4. stirringstirred for 1 hr
  5. customThe reaction was quenched by the cautious addition of water (10 mL)
  6. customThe solids were removed by filtration
  7. customthe filtrate was evaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 330 g, EtOAc in hexanes, 65% v/v, isocratic elution)

出典と根拠

ORDレコード
ord-55b4d000d50842e994804ae90d842bee
出典データセット
uspto-grants-2016_02
特許番号
US09260410B2

反応ノート

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