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Sodium hydride → (4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazol-4-yl)methanol

HRID 251456
ノート
印刷プレビュー

反応式

HRID 251456 の反応式
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][CH2:9][OH:10].[H-].[Na+].Cl[C:14]1[N:19]=[CH:18][C:17]([C:20]2[O:21][CH2:22][C:23]([CH2:26][OH:27])([CH3:25])[N:24]=2)=[CH:16][CH:15]=1>CN(C=O)C.C(OCC)(=O)C>[CH3:25][C:23]1([CH2:26][OH:27])[CH2:22][O:21][C:20]([C:17]2[CH:18]=[N:19][C:14]([O:10][CH2:9][CH2:8][CH2:7][N:3]3[CH2:4][CH2:5][CH2:6][CH:2]3[CH3:1])=[CH:15][CH:16]=2)=[N:24]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 11950723[2-(6-Chloropyridin-3-yl)-4-methyl-4,5-dihydro-1,3-oxazol-4-yl]methanolHCID 224016093-(2-Methylpyrrolidin-1-yl)propan-1-ol

生成物 1

HCID 11950724(4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazol-4-yl)methanol収率 80%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide
溶媒
2 回
HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A solution of 3-(2-methylpyrrolidin-1-yl)propan-1-ol (1.9 g, 13.4 mmol) in dry DMF (40 ml) is treated at 0° C. with sodium hydride (60% dispersion in mineral oil, 536 mg, 13.4 mmol) and stirred 15 minutes at 0° C. Then, a solution of [2-(6-chloropyridin-3-yl)-4-methyl-4,5-dihydro-1,3-oxazol-4-yl]methanol ax55 (1.8 g, 7.9 mmol) in dry DMF (40 ml) is added dropwise over 15 minutes and the resulting mixture is stirred at room temperature for 1 day. The mixture is then poured into ice-cold water (250 ml) and extracted with ethyl acetate (4×50 ml). The organic layers are combined, dried over sodium sulfate and concentrated. The residue is dried under high-vacuum with heating to leave a solid. This solid is taken up in ethyl acetate, washed with brine and filtered. After phase separation, the aqueous layer is extracted twice with ethyl acetate, the combined organic phases are washed three times with water, dried over magnesium sulfate and concentrated to afford 1.4 g of 80% pure (4-methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazol-4-yl)methanol ax56.

後処理

  1. stirringthe resulting mixture is stirred at room temperature for 1 day
  2. extractionextracted with ethyl acetate (4×50 ml)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is dried under high-vacuum
  6. temperaturewith heating
  7. customto leave a solid
  8. washwashed with brine
  9. filtrationfiltered
  10. customAfter phase separation
  11. extractionthe aqueous layer is extracted twice with ethyl acetate
  12. washthe combined organic phases are washed three times with water
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated

出典と根拠

ORDレコード
ord-be4db4661f71492eaf46b957e000474b
出典データセット
uspto-grants-2011_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07863450B2

反応ノート

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