1-(benzyloxymethyl)-1H-tetrazole → 4-((1-(benzyloxymethyl)-1H-tetrazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104953Notes

Reaction equation

HRID 2104953 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[CH:14]=[N:13][N:12]=[N:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH2:20]([O:22][C:23]1[CH:24]=[C:25]([O:40][CH:41]([CH3:43])[CH3:42])[C:26]([F:39])=[C:27]([CH:38]=1)/[CH:28]=[N:29]/[C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=1)[CH3:21]>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[C:14]([N:29]([CH2:28][C:27]2[CH:38]=[C:23]([O:22][CH2:20][CH3:21])[CH:24]=[C:25]([O:40][CH:41]([CH3:43])[CH3:42])[C:26]=2[F:39])[C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=2)=[N:13][N:12]=[N:11]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 106315241-(benzyloxymethyl)-1H-tetrazoleHCID 178418339ButyllithiumHCID 178466720HCID 178466720, compound

Product 1

HCID 688162584-((1-(benzyloxymethyl)-1H-tetrazol-5-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrileYield 24.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of Intermediate 12.1 (50.0 mg, 0.263 mmol) in 2 mL THF at −78° C. was added 1.6 M solution of BuLi in THF (181 μL, 0.289 mmol). The mixture was stirred at −78° C. for 2 min, then a solution of Intermediate 7.3 (86 mg, 0.263 mmol) in 0.6 mL THF was added dropwise. The mixture was stirred at −78° C. for 30 min, was allowed to warm to rt over 1 h, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (25 to 30% EtOAc/hexanes, stepwise gradient) to afford 33 mg of Intermediate 12.2 as yellow residue.

Workup

  1. stirringThe mixture was stirred at −78° C. for 30 min
  2. temperatureto warm to rt over 1 h
  3. customwas quenched with sat. NH4Cl
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (25 to 30% EtOAc/hexanes, stepwise gradient)

Sources & evidence

ORD record
ord-3e94b99a5adc492fbcab42fc6c24c872
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

Loading…