Sodium hydride → HCID 68612036, compound

HRID 2095314Notes

Reaction equation

HRID 2095314 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@H:15]2[CH2:17][C@@H:16]2[CH2:18][OH:19])[CH:12]=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br.Br[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1.[NH4+].[Cl-]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:8][C:9]1[CH:14]=[N:13][CH:12]=[C:11]([C@H:15]2[CH2:17][C@@H:16]2[CH2:18][O:19][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 56951230HCID 56951230, compound

Product 1

HCID 68612036HCID 68612036, compoundYield 88.6%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (1S,2S)-2-[5-(benzyloxy)-3-pyridyl]cyclopropylmethanol (150 mg, 0.59 mmol) in anhydrous THF (5 mL) in a 25 mL round-bottom flask was added sodium hydride (60% dispersion in mineral oil, 57 mg, 1.41 mmol, 2.4 equiv.). The flask was equipped with a condenser, and the atmosphere was exchanged with Ar (3 times). The suspension was stirred at room temperature for 2 h. 2-(Bromomethyl)pyridine hydrobromide (178 mg, 0.70 mmol, 1.2 equiv.) and tetra-n-butylammonium iodide (23 mg, 60 μmol, 0.1 equiv.) in dry THF (2 mL) were added. The resulting mixture was again protected with Ar and was stirred at room temperature overnight. Saturated NH4Cl solution (15 mL) was added to quench excessive sodium hydride, and the product was extracted into EtOAc (3×20 mL). The combined organic phases were washed with brine (15 mL), dried over Na2SO4, and concentrated. The residue was purified by CC on SiO2 (25×1.0 cm, EtOAc) to give the crude product as a colorless oil (181 mg, 88%). MS (EI) m/z 346 (M+, 6.8%).

Workup

  1. customThe flask was equipped with a condenser
  2. stirringwas stirred at room temperature overnight
  3. customto quench excessive sodium hydride
  4. extractionthe product was extracted into EtOAc (3×20 mL)
  5. washThe combined organic phases were washed with brine (15 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by CC on SiO2 (25×1.0 cm, EtOAc)

Sources & evidence

ORD record
ord-8cf83d712eb847b299a99230c4dc86f8
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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