Ethyl bromoacetate → Ethyl (5-{3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate

HRID 561211Notes

Reaction equation

HRID 561211 reaction equation
[Br:1][C:2]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:15]=[C:14]([C:16]3[NH:20][N:19]=[N:18][N:17]=3)[O:13][N:12]=2)[CH2:7][CH2:6]1.Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].C(N(CC)CC)C>C1COCC1.O>[Br:1][C:2]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:15]=[C:14]([C:16]3[N:17]=[N:18][N:19]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:20]=3)[O:13][N:12]=2)[CH2:7][CH2:6]1

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 8471TriethylamineHCID 178505486HCID 178505486, compound

Product 1

HCID 53388532Ethyl (5-{3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-(2-bromo-5-fluorophenoxy)-1-[5-(1H-tetrazol-5-yl)isoxazol-3-yl]piperidine (1.2 g, 2.93 mmol), ethyl bromoacetate (0.45 mL, 4.04 mmol) and triethylamine (0.75 mL, 5.38 mmol) in THF (12 mL) was heated at reflux temperature for 2 h. After cooling, the mixture was diluted with water and extracted with EtOAc. The EtOAc extract was washed with water, dried (Na2SO4) and concentrated. Combi-Flash chromatography (40 g, 25-40% EtOAc in hexanes for 20 min, 35 mL/min, 18 mL/fraction) gave the title compound as a colorless gum, containing about 20% of 1-alkylated isomer.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 2 h
  3. temperatureAfter cooling
  4. extractionextracted with EtOAc
  5. extractionThe EtOAc extract
  6. washwas washed with water
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-09466d828cb64031b9a8b0fafde4e685
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

Loading…