2,3,4,5,6-Pentachlorophenyl 4-[3-(1-piperidinyl)propoxy]benzoate → HCID 17986317, compound

HRID 268737Notes

Reaction equation

HRID 268737 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:30]=[CH:29][C:14]([C:15]([O:17]C3C([Cl:24])=C(Cl)C(Cl)=C(Cl)C=3Cl)=O)=[CH:13][CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([N:38]1[CH2:46][C:45]2[C:40](=[CH:41][CH:42]=[CH:43][C:44]=2[F:47])[CH2:39]1)C1C=CC=CC=1>CC(O)C.[OH-].[OH-].[Pd+2]>[ClH:24].[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([C:15]([N:38]3[CH2:46][C:45]4[C:40](=[CH:41][CH:42]=[CH:43][C:44]=4[F:47])[CH2:39]3)=[O:17])=[CH:29][CH:30]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 179862702,3,4,5,6-Pentachlorophenyl 4-[3-(1-piperidinyl)propoxy]benzoateHCID 17986315HCID 17986315, compound

Product 1

HCID 17986317HCID 17986317, compoundYield 17.6%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 3776IsopropanolSolvent

Procedure

A mixture of pentachlorophenyl 4-(3-piperdin-1-ylpropoxy)benzoate (D10) (500 mg) and N-benzyl-4-fluoroisoindoline (D9) (200 mg) in IPA (10 ml) at rt was treated with poly(methylhydrosiloxane) (0.16 ml) and palladium hydroxide on carbon (30 mg, 20% Pd) and stirred overnight. The mixture was filtered and evaporated. The residue was redissolved in EtOAc (20 ml), washed with saturated sodium hydrogen carbonate solution (10 ml), water (2×10 ml), brine (10 ml), dried (MgSO4) and evaporated. The residue was chromatographed on a silica gel flash column [step gradient 2-8% MeOH (containing 10% 0.880 ammonia solution) in DCM]. The required fractions were evaporated, then redissolved in DCM and treated with excess 4M HCl in dioxan. The title compound (E55) (65 mg) was obtained by crystallisation from acetone. MS electrospray (+ion) 383 (MH+). 1H NMR δ (DMSO-d6): 10.15 (1H, m), 7.09-7.65 (7H, m),4.89 (4H, m), 4.13 (2H, t, J=6 Hz), 3.46 (2H, m), 3.16 (2H, m), 2.90 (2H, m), 2.22 (2H, m), 1.79 (5H, m), 1.42 (1H, m).

Workup

  1. filtrationThe mixture was filtered
  2. customevaporated
  3. dissolutionThe residue was redissolved in EtOAc (20 ml)
  4. washwashed with saturated sodium hydrogen carbonate solution (10 ml), water (2×10 ml), brine (10 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was chromatographed on a silica gel flash column [step gradient 2-8% MeOH (containing 10% 0.880 ammonia solution) in DCM]
  8. customThe required fractions were evaporated
  9. dissolutionredissolved in DCM
  10. additiontreated with excess 4M HCl in dioxan

Sources & evidence

ORD record
ord-1f6432b5563c47c882ab5044ccef738c
Source dataset
uspto-grants-2008_11
Patent number
US07446103B2

Reaction notes

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