Methyl iodide → HCID 67094875, compound

HRID 1809133Notes

Reaction equation

HRID 1809133 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]2[O:11][CH2:12][C@H:13]([CH2:22][OH:23])[N:14]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][N:16]=3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].[CH3:24]OC(C1C2OC[C@H](CO)N(C3C=CC(CC)=CN=3)C=2C=CC=1)=O.[H-].[Na+].CI>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[C:10]2[O:11][CH2:12][C@H:13]([CH2:22][O:23][CH3:24])[N:14]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][N:16]=3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67054028HCID 67054028, compoundHCID 67094854HCID 67094854, compound

Product 1

HCID 67094875HCID 67094875, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3.0 g (9.5 mmol) of (S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-carboxylic acid methyl ester (compound 22) obtained in (34-6) were dissolved in 50 mL of THF. The solution was cooled to 0° C. and 1.1 g (28.6 mmol) of NaH was added slowly. The solution was stirred at 0° C. for 10 min and then at room temperature for 5 min. The solution was re-cooled to 0° C. and 120 uL (19.1 mmol) of MeI was added slowly. The mixture was placed at the same temperature for 1-2 hr and stirred while heating to room temperature. When the reaction terminated, the reaction mixture was neutralized by slow addition of 1N HCl solution, and dissolved in ethyl acetate and washed with distilled water and saturated sodium chloride solution, followed by drying over magnesium sulfate and concentration under reduced pressure. The resulting residue was subjected to column chromatography (ethyl acetate/hexane=1/2) to obtain the title compound (2.7 g, yield: 85%).

Workup

  1. waitat room temperature for 5 min
  2. temperatureThe solution was re-cooled to 0° C.
  3. waitThe mixture was placed at the same temperature for 1-2 hr
  4. stirringstirred
  5. temperaturewhile heating to room temperature
  6. customWhen the reaction terminated
  7. additionthe reaction mixture was neutralized by slow addition of 1N HCl solution
  8. dissolutiondissolved in ethyl acetate
  9. washwashed with distilled water and saturated sodium chloride solution
  10. dry with materialby drying over magnesium sulfate and concentration under reduced pressure

Sources & evidence

ORD record
ord-1c4a2addef094b1cb6d3921cbfbf3a7a
Source dataset
uspto-grants-2013_01
Patent number
US08362012B2

Reaction notes

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