Acetic Acid → 1-[1-(2-Fluorophenethyl)piperidin-4-yl]-6-bromoindoline

HRID 1790504Notes

Reaction equation

HRID 1790504 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][CH:24]=[CH:23][C:13]=1[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1.C(O)(=O)C.[OH-].[Na+]>ClCCCl.C(OCC)(=O)C>[F:11][C:12]1[CH:26]=[CH:25][CH:24]=[CH:23][C:13]=1[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=3)[CH2:6][CH2:7]2)[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 114133861-(2-Fluorophenethyl)piperidin-4-oneHCID 130983796-Bromo-2,3-dihydro-1H-indole

Product 1

HCID 220380011-[1-(2-Fluorophenethyl)piperidin-4-yl]-6-bromoindolineYield 66.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triacetoxylated sodium borohydride (15.0 g) was added under ice cooling to a liquid mixture of 6-bromoindoline (9.0 g), 1-(2-fluorophenethyl)piperidin-4-one (11.0 g) and acetic acid (12.5 ml) in 1,2-dichloroethane (140 ml). Then the reaction mixtures were stirred at room temperature overnight. The reaction mixtures were diluted with ethyl acetate (400 ml) and then an 8 N aqueous solution (70 ml) of sodium hydroxide was added thereto. The organic layer was separated, extracted with 5 N hydrochloric acid (100 ml) and then basified with an 8 N aqueous solution of sodium hydroxide. Then it was extracted with ethyl acetate and washed successively with water and brine. The ethyl acetate layer was dried over magnesium sulfate and the solvent was evaporated distilled off under reduced pressure to give the title compound (12.2 g) as a pale yellow solid (yield: 66.6%). 2.10(2H,dt,J=7.6,2.8 Hz), 2.48-2.53(2H,m), 2.77(2H,t, J=8.4 Hz), 2.83(2H,t,J=8.4 Hz), 2.96-3.03(2H,br-d), 3.37(2H,t,J=8.4 Hz), 3.34-3.43(1H,m), 6.57(1H,d,J=1.2 Hz), 6.61(1H,dd,J=7.6,1.2 Hz), 6.90(1H,d,J=7.6 Hz), 7.10-7.16(2H,m), 7.21-7.28(1H,m), 7.33(1H,dt,J=7.6,1.2 Hz).

Workup

  1. customThen the reaction mixtures
  2. customThe reaction mixtures
  3. customThe organic layer was separated
  4. extractionextracted with 5 N hydrochloric acid (100 ml)
  5. extractionThen it was extracted with ethyl acetate
  6. washwashed successively with water and brine
  7. dry with materialThe ethyl acetate layer was dried over magnesium sulfate
  8. customthe solvent was evaporated
  9. distillationdistilled off under reduced pressure

Sources & evidence

ORD record
ord-40652b9569aa48bbac61ef803c67c712
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

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