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

HRID 2185759

Reaction equation

HRID 2185759 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

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) δ1.40 (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)+.

Workup

  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)

Sources & evidence

ORD record
ord-337f5c26db214065a1bdcc026b996127
Source dataset
uspto-grants-2002_06
Patent number
US06403575B1

Linked notes

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