Potassium Hydroxide → 5-Benzyloxy-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

HRID 367093ノート

反応式

HRID 367093 の反応式
[CH2:1]([O:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([OH:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:16].[K+].[C:18]([C@@H:25]1[CH2:28][CH2:27][N:26]1[CH2:29][O:30]S(C1C(C)=CC=CC=1)(=O)=O)(OC(C)(C)C)=O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:18][C@@H:25]2[CH2:28][CH2:27][N:26]2[C:29]([O:30][C:2]([CH3:7])([CH3:3])[CH3:1])=[O:16])[CH:12]=[N:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 14797Potassium HydroxideHCID 229897043-Benzyloxy-5-hydroxypyridineHCID 86755944Boc-(S)-toluensulfonyloxymethylazetidine

生成物 1

HCID 213451995-Benzyloxy-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine収率 178.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
80 °C

実験手順

Next, a solution of 3-benzyloxy-5-hydroxypyridine (350 mg, 1.74 mmol, from step 120d) in DMF (20 mL) was treated with ground KOH (154 mg, 2.74 mmol) and stirred for 30 minutes at 80° C. To this mixture was rapidly added the Boc-(S)-toluensulfonyloxymethylazetidine (585 mg, 1.74 mmol) dissolved in DMF (5 mL), and the mixture was stirred for 16 hours at 80° C. The mixture was concentrated under vacuum to remove the DMF, and the residue was diluted with water and extracted with EtOAc. The organic extracts were combined, dried (Na2SO4), filtered, and concentrated under vacuum to give 800 mg of crude product. This material was purified by chromatography (silica gel; hexane/EtOAc, 10:1) to give the title compound (575 mg, 90%): 1H NMR (CDCl3, 300 MHz) δ 1.40 (s, 9H), 2.26-2.30 (m, 2H), 3.90-2.94 (m, 2H), 4.16 (m, 1H), 4.35 (m, 1H), 4.54 (m, 1H), 5.10 (s, 2H), 6.95 (s, 1H), 7.40-7.46 (m, 5H), 8.20 (br s, (2H): MS (CI/NH3) m/z: 371 (M+H)+.

後処理

  1. stirringthe mixture was stirred for 16 hours at 80° C
  2. concentrationThe mixture was concentrated under vacuum
  3. customto remove the DMF
  4. additionthe residue was diluted with water
  5. extractionextracted with EtOAc
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customto give 800 mg of crude product
  10. customThis material was purified by chromatography (silica gel; hexane/EtOAc, 10:1)

出典と根拠

ORDレコード
ord-99a4d43e91f14a3e82dee4fb5f87dcce
出典データセット
uspto-grants-2000_10
特許番号
US06133253

反応ノート

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