Methyl iodide → 7-N-(tert-Butoxycarbonyl)-8-methyl-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

HRID 133065Notes

Reaction equation

HRID 133065 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21]N(CCN(C)C)C.C([Li])CCC.IC>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:18])([F:19])[F:20])[N:16]=[C:10]2[CH:9]1[CH3:21])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 53393358tert-Butyl 2-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazine-7(8H)-carboxylateHCID 178418339Butyllithium

Product 1

HCID 693627227-N-(tert-Butoxycarbonyl)-8-methyl-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 7-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine (1.85 g, 6.35 mmol) in 25 mL of toluene at −78° C. was added N,N,N,N-tetramethylethylenediamine (1.01 mL, 6.67 mmol) followed by n-butyllithium (4.17 mL of a 1.6 M solution in hexanes, 6.67 mmol). The mixture was stirred at −78° C. for 10 min and then iodomethane (0.415 mL, 6.67 mmol) was added dropwise. The mixture was allowed to stir at −78° C. for 10 min, and then it was warmed to ambient temperature. The reaction was quenched with aqueous ammonium chloride and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated. Purification by flash chromatography (silica gel, 10% ethyl acetate/hexane) yielded the title compound.

Workup

  1. stirringto stir at −78° C. for 10 min
  2. temperatureit was warmed to ambient temperature
  3. customThe reaction was quenched with aqueous ammonium chloride
  4. extractionthe aqueous layer was extracted three times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customPurification by flash chromatography (silica gel, 10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3cc87cf6423f45f8bcd50184469a3bd6
Source dataset
uspto-grants-2008_06
Patent number
US07390809B2

Reaction notes

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