Water → Cyclohexyl(phenyl)[1-(pyrrolidin-1-ylmethyl)-1H-1,2,4-triazol-5-yl]methanol

HRID 2383377Notes

Reaction equation

HRID 2383377 reaction equation
[N:1]1([CH2:6][N:7]2[CH:11]=[N:10][CH:9]=[N:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])CCC.[CH:17]1([C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.O>O1CCCC1>[CH:25]1([C:23]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)([C:11]2[N:7]([CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[N:8]=[CH:9][N:10]=2)[OH:24])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]1

Participants

6

Reactant 4

HCID 962WaterHCID 12837Cyclohexyl phenyl ketoneHCID 38457621-(pyrrolidin-1-ylmethyl)-1H-1,2,4-triazoleHCID 178418339Butyllithium

Product 1

HCID 59145963Cyclohexyl(phenyl)[1-(pyrrolidin-1-ylmethyl)-1H-1,2,4-triazol-5-yl]methanolYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(pyrrolidin-1-ylmethyl)-1H-1,2,4-triazole (Preparation 16, 12.0 g, 78.84 mmol) was dissolved in tetrahydrofuran (120 mL) and the solution cooled to −78° C. n-Butyl lithium (2.5M in hexanes, 34.7 ml, 86.7 mmol) was then added dropwise over 30 mins. After warming to room temperature and stirring for 1 hour the reaction mixture was cooled to −78° C. and a solution of cyclohexyl(phenyl)methanone (16.3 g, 86.7 mmol) in tetrahydrofuran (30 mL) added dropwise. After warming to room temperature over 18 hr, water (100 ml) was added and the solvent removed in vacuo. The residue was partitioned with ethyl acetate (200 ml), the aqueous phase separated and re-extracted with ethyl acetate (2×200 ml). The combined organic layers were dried over magnesium sulphate, filtered and the solvent removed in vacuo to furnish the title compound as a yellow oil, in 100% yield, 27.28 g.

Workup

  1. additionwas then added dropwise over 30 mins
  2. temperaturewas cooled to −78° C.
  3. temperatureAfter warming to room temperature over 18 hr
  4. customthe solvent removed in vacuo
  5. customThe residue was partitioned with ethyl acetate (200 ml)
  6. customthe aqueous phase separated
  7. extractionre-extracted with ethyl acetate (2×200 ml)
  8. dry with materialThe combined organic layers were dried over magnesium sulphate
  9. filtrationfiltered
  10. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-b1872d3100d34d0797f3fdcd3b1c4562
Source dataset
uspto-grants-2012_09
Patent number
US08263623B2

Reaction notes

Loading…