Potassium Hydroxide → HCID 46175647, compound

HRID 455978Notes

Reaction equation

HRID 455978 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]([F:15])([F:14])[F:13])=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[OH-].[K+].[CH3:18][O:19][CH2:20][CH2:21]Br>CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]([F:15])([F:13])[F:14])=[C:6]2[C:10]=1[N:9]([CH2:21][CH2:20][O:19][CH3:18])[CH:8]=[CH:7]2

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 809722-Bromoethyl methyl etherHCID 46175564HCID 46175564, compound

Product 1

HCID 46175647HCID 46175647, compoundYield 95.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 5 (16 g, 72.8 mmol) and powder KOH (20.4 g, 364.2 mmol) in DMSO (150 mL) is stirred at rt for 10 min. 2-Methoxyethyl bromide (10.3 mL, 109.2 mmol) is added. This mixture is stirred at rt overnight. LC/MS indicates the reaction is completed. The mixture is partitioned between H2O and Et2O. The two layers are separated, and the aqueous layer is extracted with Et2O (2×). The combined organic layers are washed with H2O and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude material is purified on silica gel with heptane/EtOAc (100/0 to 50/50) as eluant to give 19.3 g (95%) of 6 as a yellow liquid. 1H NMR (CDCl3) δ 7.15 (d, J=2.1 Hz, 1H), 6.90-6.75 (m, 2H), 6.56 (t, J=2.5 Hz, 1H), 3.72 (t, J=5.2 Hz, 2H), 3.72 (t, J=5.2 Hz, 2H), 3.31 (s, 3H); 19F NMR (CDCl3) δ −57.54 (s, 3F), −137.00 (d, J=11.3 Hz, 1F); MS 278 (M+1, 100%).

Workup

  1. stirringThis mixture is stirred at rt overnight
  2. customThe mixture is partitioned between H2O and Et2O
  3. customThe two layers are separated
  4. extractionthe aqueous layer is extracted with Et2O (2×)
  5. washThe combined organic layers are washed with H2O and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material is purified on silica gel with heptane/EtOAc (100/0 to 50/50) as eluant

Sources & evidence

ORD record
ord-caeaad45c57f408eada70977fc0ca9dc
Source dataset
uspto-grants-2013_07
Patent number
US08497379B2

Reaction notes

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