Triethylamine → Methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinate

HRID 72429

反応式

HRID 72429 の反応式
Cl.[OH:2][CH:3]1[CH2:6][NH:5][CH2:4]1.C(N(CC)CC)C.Cl[C:15]1[N:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:16]=1[C:17]([O:19][CH3:20])=[O:18]>O1CCCC1.CO>[Cl:25][C:22]1[CH:23]=[N:24][C:15]([N:5]2[CH2:6][CH:3]([OH:2])[CH2:4]2)=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]

参加物

5

反応物 3

HCID 8471Triethylamine2 回HCID 27592903-Hydroxyazetidine hydrochloride2 回HCID 2764318Methyl 2,5-Dichloronicotinate

生成物 1

HCID 67958303Methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinate収率 76.6%

試薬・触媒・溶媒 1

HCID 21899815MeOH tetrahydrofuran溶媒

反応条件

温度
75 °C

実験手順

To a mixture of 3-Hydroxyazetidine hydrochloride (37.17 g, 0.339 mol) and triethylamine (70.93 ml, 0.508 mol) in tetrahydrofuran/methanol (840/280 ml) Methyl 2,5-dichloronicotinate (70 g, 0.339 mol) was added and the resulting mixture was heated at 75° C. for 4 hours then at 62° C. overnight. 3-Hydroxyazetidine hydrochloride (3.7 g, 0.03 mol) and triethylamine (23.60 ml, 0.16 mol) were added and the reaction mixture was further heated at 80° C. for 28 h. Solvents were evaporated in vacuo. The residue was taken in dichloromethane (400 ml) and water (500 ml). The formed solid was filtered, washed with water (500 ml) and dried in vacuum to afford a first batch of the title compound (D62) (63 g).

後処理

  1. additionwas added
  2. customat 62° C.
  3. customovernight
  4. temperaturethe reaction mixture was further heated at 80° C. for 28 h
  5. customSolvents were evaporated in vacuo
  6. filtrationThe formed solid was filtered
  7. washwashed with water (500 ml)
  8. customdried in vacuum

出典と根拠

ORDレコード
ord-25e4a4f6a52f415abe7623234769fe0c
出典データセット
uspto-grants-2014_09
特許番号
US08828987B2

関連ノート

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