1,1-Dichloroethane → 1-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-bromoindoline

HRID 1790437Notes

Reaction equation

HRID 1790437 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][NH:8]2)=[CH:4][CH:3]=1.[F:11][C:12]1[CH:26]=[CH:25][C:15]([CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]2)=[CH:14][CH:13]=1.ClC(Cl)C>C(O)(=O)C>[F:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][CH:21]([N:8]3[C:9]4[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=4)[CH2:6][CH2:7]3)[CH2:20][CH2:19]2)=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 63651,1-DichloroethaneHCID 70235941-[2-(4-Fluorophenyl)ethyl]piperidin-4-oneHCID 130983796-Bromo-2,3-dihydro-1H-indole

Product 1

HCID 220378891-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-bromoindolineYield 58%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Triacetoxylated sodium borohydride (298 g) was added over 30 min to a mixture of 6-bromoindoline (175 g), 1-(4-fluorophenethyl)-4-piperidone (194 g), acetic acid (250 ml) and dichloroethane (2.5 l) followed by stirring 2 hr. Then the reaction solution was concentrated under reduced pressure, diluted with ethyl acetate (2 l), an 8 N aqueous solution of sodium hydroxide (1 l) and water (500 ml) and the layers were separated. The organic layer was washed successively with water (0.5 l) and brine (0.5 l), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in hot ethyl acetate (500 ml) and then cooled with ice water. The resulting crystalline precipitates were collected by filtration to give the title compound (205 g) (yield: 58%).

Workup

  1. concentrationThen the reaction solution was concentrated under reduced pressure
  2. additiondiluted with ethyl acetate (2 l)
  3. customan 8 N aqueous solution of sodium hydroxide (1 l) and water (500 ml) and the layers were separated
  4. washThe organic layer was washed successively with water (0.5 l) and brine (0.5 l)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting residue was dissolved in hot ethyl acetate (500 ml)
  8. temperaturecooled with ice water
  9. customThe resulting crystalline precipitates
  10. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-b859a7b4953a47449466d6cd502ab05c
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

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