Ethyl 2-hydroxyisobutyrate → Bindarit

HRID 1803404ノート

反応式

HRID 1803404 の反応式
C([O:3][C:4](=[O:9])[C:5]([OH:8])([CH3:7])[CH3:6])C.[H-].[Na+].[CH2:12]([N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([CH2:28]Cl)=[N:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C>[CH2:12]([N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([CH2:28][O:8][C:5]([CH3:6])([CH3:7])[C:4]([OH:3])=[O:9])=[N:20]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

参加物

7

反応物 4

HCID 6653Ethyl 2-hydroxyisobutyrateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 532606481-Benzyl-3-(chloromethyl)-1H-indazole

生成物 1

HCID 71354Bindarit

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒2 回HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
90 °C

実験手順

Ethyl-2-hydroxyisobutyrate (18.5 g, 140 mmol, 1.2 eq.), toluene (100 mL) and DMF (20 mL) were placed in a three-necked flask fitted with a mechanical stirrer and a reflux condenser under an inert atmosphere. A dispersion of 60% NaH (5.6 g, 140 mmol, 1.2 eq.) was added to the mixture in portions over a period of approximately 1.5 hours. A solution of 1-benzyl-3-chloromethyl-1H-indazole (30 g, 117 mmol, 1 eq.) in toluene (90 mL) and DMF (60 mL) was then added dropwise. The reaction mixture was heated to approximately 90° C. and kept at that temperature until the reaction was complete (checked by TLC, approximately 10 hours). After cooling to room temperature the mixture was washed with acidified water and water. The organic phase was concentrated under reduced pressure and the oily residue obtained was treated with 10 M NaOH (36 mL) at reflux temperature for at least 3 hours. The product, which was precipitated out by the addition of concentrated HCl, was filtered and dried. Yield: 32.3 g of white solid (85%).

後処理

  1. customfitted with a mechanical stirrer and a reflux condenser under an inert atmosphere
  2. custom(checked by TLC, approximately 10 hours)
  3. temperatureAfter cooling to room temperature the mixture
  4. washwas washed with acidified water and water
  5. concentrationThe organic phase was concentrated under reduced pressure
  6. customthe oily residue obtained
  7. temperatureat reflux temperature for at least 3 hours
  8. customThe product, which was precipitated out by the addition of concentrated HCl
  9. filtrationwas filtered
  10. customdried

出典と根拠

ORDレコード
ord-8051e514f88845b08a3bf09e8656c363
出典データセット
uspto-grants-2013_01
特許番号
US08350052B2

反応ノート

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