Water → HCID 14326455, compound

HRID 35742Notes

Reaction equation

HRID 35742 reaction equation
[OH:1][CH2:2][CH:3]1[O:7][N:6]([CH3:8])[C:5]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)([CH2:9][N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)[CH2:4]1.[H-].[Na+].[CH3:24]I.O>O1CCCC1>[CH3:24][O:1][CH2:2][CH:3]1[O:7][N:6]([CH3:8])[C:5]([C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)([CH2:9][N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)[CH2:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14326454HCID 14326454, compound

Product 1

HCID 14326455HCID 14326455, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

5-(Hydroxymethyl)-3-(4-chlorophenyl)-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidine (3: R1 =4-Cl, R2 =H) 2.50 g, 8 mmol) is added to a suspension of 1.32 g (24 mmol) of 50% by weight sodium hydride in 50 ml anhydrous tetrahydrofuran, at 0° C. under a nitrogen atmosphere. After stirring for 1 hour at 0° C., 1.28 g (9 mmol) of methyl iodide is added and the resulting suspension is heated to reflux and stirred for 20 hours. Upon cooling to room temperature, the reaction mixture is poured into 100 ml of water and then extracted with chloroform (3×75 ml). The combined organic extracts are dried over anhydrous magnesium sulfate and the solvent removed under reduced pressure. The crude residue is flash-chromatographed on neutral silica gel using chloroform-methanol (98:2 by volume) as eluent. Following crystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3) are obtained, mp 123°-126° C.

Workup

  1. temperaturethe resulting suspension is heated
  2. temperatureto reflux
  3. stirringstirred for 20 hours
  4. temperatureUpon cooling to room temperature
  5. extractionextracted with chloroform (3×75 ml)
  6. dry with materialThe combined organic extracts are dried over anhydrous magnesium sulfate
  7. customthe solvent removed under reduced pressure
  8. customThe crude residue is flash-chromatographed on neutral silica gel
  9. customcrystallization from ethyl acetate, 1.67 g (64%) of compound 3 (R1 =4-Cl, R2 =CH3)
  10. customare obtained

Sources & evidence

ORD record
ord-dde84b7759df4b9485c17f6e0b1dd693
Source dataset
uspto-grants-1988_08
Patent number
US04767867

Reaction notes

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