2-Fluoroethyl bromide → HCID 86601517, compound

HRID 968641Notes

Reaction equation

HRID 968641 reaction equation
[H-].[Na+].[CH:3]1([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[OH:19])[C:12]([C:20]([N:22]3[CH2:27][CH2:26][N:25]([CH2:28][CH3:29])[CH2:24][CH2:23]3)=[O:21])=[CH:11]2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:31][CH2:32][F:33]>CN(C)C=O>[CH:3]1([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:19][CH2:31][CH2:32][F:33])[C:12]([C:20]([N:22]3[CH2:23][CH2:24][N:25]([CH2:28][CH3:29])[CH2:26][CH2:27]3)=[O:21])=[CH:11]2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 129822-Fluoroethyl bromideHCID 24758Sodium hydrideHCID 69490985HCID 69490985, compound

Product 1

HCID 86601517HCID 86601517, compoundYield 18.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 65 mg, 1.62 mmol) was added portionwise with stirring under a stream of nitrogen to a solution of 4-{[1-(cyclohexylmethyl)-7-hydroxy-1H-indole-3-yl]carbonyl}-1-ethylpiperazine (200 mg, 0.54 mmol) in dimethylformamide (5 ml). After 30 minutes, 1-bromo-2-fluoroethane (49 μl, 0.65 mmol) was added. The mixture was heated to 60° C. with stirring for 48 hours. The reaction was quenched with 2-propanol (10 ml) and then concentrated. The resulting brown gum was partitioned between dichloromethane (50 ml) and 5% sodium hydrogen carbonate solution (50 ml). The organic layer was washed with water (50 ml), dried over sodium sulfate and concentrated. The crude intermediate was purified by flash chromatography using 95% dichloromethane, 5% methanol as eluent to afford the title compound (54 mg, 0.1 mmol). 1H NMR (400 MHz, CD3OD) δH 1.05 (2H, m), 1.19 (3H, m), 1.39 (3H, t, J 7.5), 1.56 (2H, m), 1.69 (3H, m), 1.92 (1H, m), 2.48 (2H, q, J 7.0), 2.53 (4H, m), 3.75 (4H, t, J 5.0), 4.26 (2H, d, J 7.5), 4.32 (1H, m), 4.39 (1H, m), 4.75 (1H, m), 4.87 (1H, m), 6.73 (1H, d, J 8.0), 7.06 (1H, t, J 8.0), 7.26 (1H, d, J 8.0), 7.44 (1H, s); EIMS: m/z=416.2 [M+H]+.

Workup

  1. customThe reaction was quenched with 2-propanol (10 ml)
  2. concentrationconcentrated
  3. customThe resulting brown gum was partitioned between dichloromethane (50 ml) and 5% sodium hydrogen carbonate solution (50 ml)
  4. washThe organic layer was washed with water (50 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude intermediate was purified by flash chromatography

Sources & evidence

ORD record
ord-7af4f76c233e4da7ac21352372afaacf
Source dataset
uspto-grants-2007_12
Patent number
US07304064B2

Reaction notes

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