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

HRID 367093

반응식

HRID 367093 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
80 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-99a4d43e91f14a3e82dee4fb5f87dcce
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06133253

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