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

HRID 1916794ノート

反応式

HRID 1916794 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.O>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

5

反応物 3

HCID 962WaterHCID 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

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 (10) (WO 2007089512) (10.0 g, 35.7 mmol) under nitrogen in THF (100 mL), at −78° C., was added DIBAL (1M solution in THF, 71.3 mL, 71.3 mmol) over 1 hr. The reaction mixture was stirred at −78 to −60° C. for 40 min and then warmed to −15° C. over 1 hr. The solution was re-cooled to −78° C. and treated with further DIBAL (1M solution in THF, 35 mL, 35.7 mmol). The mixture was allowed to warm to −40° C. and stirred for 1 hr. Water (10 mL) was added cautiously to quench the reaction followed by MgSO4 (20 g) and the solids removed by filtration. The filtrate was concentrated to dryness under reduced pressure and the residue subjected to column chromatography (330 g), eluting with 65% EtOAc in hexanes to give tert-butyl 4-(2-hydroxyethyl)pyridin-2-ylcarbamate (11) (6.00 g, 64%) as a yellow solid: m/z 239 (M+H)+ (ES+).

後処理

  1. temperaturewarmed 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. customto quench the reaction
  6. customthe solids removed by filtration
  7. concentrationThe filtrate was concentrated to dryness under reduced pressure
  8. washeluting with 65% EtOAc in hexanes

出典と根拠

ORDレコード
ord-7966537b430b43068d2ee4be06f6735d
出典データセット
uspto-grants-2013_12
特許番号
US08618140B2

反応ノート

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