Hexane → HCID 66855678, compound

HRID 1530097Notes

Reaction equation

HRID 1530097 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:13]2[N:17]=[CH:16][N:15]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[N:14]=2)=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:6]=1.C([Li])CCC.CCCCCC.CON(C)[C:38](=[O:40])[CH3:39]>C1COCC1.CC(O)=O>[C:7]1([C:5]2[N:6]=[C:2]([CH2:1][C:38]([CH3:39])=[O:40])[S:3][C:4]=2[C:13]2[N:17]=[CH:16][N:15]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[N:14]=2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 537505N-Methoxy-N-methylacetamideHCID 66855639HCID 66855639, compoundHCID 178418339Butyllithium

Product 1

HCID 66855678HCID 66855678, compoundYield 77.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(2-methyl-4-phenyl-1,3-thiazol-5-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazole (32.6 g, 100 mmol) in THF (1.8 L), was dropwise added 1.6M solution of n-butyllithium in hexane (150 mL, 240 mmol) at −78° C. over 1 h, and the mixture was stirred for 1 h at the same temperature. To the reaction mixture was dropwise added a solution of N-methoxy-N-methylacetamide (10.3 g, 100 mmol) in THF (600 mL) at −78° C. over 3 h. After addition, the mixture was stirred for 30 min at the same temperature. The reaction mixture was neutralized by the addition of AcOH (13.8 mL), and the mixture was allowed to warm to rt. The solvent was evaporated under reduced pressure and then, to the residue, were added EtOAc (400 mL) and saturated aqueous ammonium chloride (300 mL). The aqueous layer was extracted with EtOAc, the combined organic layer was washed with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, and then insoluble materials were removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (EtOAc/hexane=5/95→80/20) to give the title compound (28.4 g, 74%) as a pale yellow oil.

Workup

  1. customat −78° C.
  2. customover 1 h
  3. additionAfter addition
  4. stirringthe mixture was stirred for 30 min at the same temperature
  5. customThe solvent was evaporated under reduced pressure
  6. additionto the residue, were added EtOAc (400 mL) and saturated aqueous ammonium chloride (300 mL)
  7. extractionThe aqueous layer was extracted with EtOAc
  8. washthe combined organic layer was washed with saturated aqueous ammonium chloride
  9. dry with materialdried over anhydrous magnesium sulfate
  10. custominsoluble materials were removed by filtration
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (EtOAc/hexane=5/95→80/20)

Sources & evidence

ORD record
ord-bc35157cb89348288aa4d204fb68e4e1
Source dataset
uspto-grants-2015_07
Patent number
US09090601B2

Reaction notes

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