Sodium Iodide → HCID 66611341, compound

HRID 2280389Notes

Reaction equation

HRID 2280389 reaction equation
[CH2:1]([NH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][C:10]1([F:16])[F:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[Na+].C(N(CC)CC)C.Cl[CH2:27][CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1>>[CH2:1]([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([CH2:27][CH2:28][CH2:29][O:30][C:31]2[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=2)[CH2:11][C:10]1([F:16])[F:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 5238Sodium IodideHCID 8471Triethylamine2×HCID 743911-(3-Chloropropoxy)-4-fluorobenzene2×HCID 46177418HCID 46177418, compound

Product 1

HCID 66611341HCID 66611341, compoundYield 49%

Conditions

Temperature
120 °C

Procedure

In a 100 mL flask, a mixture of 1.22 g (5.4 mmol) of benzyl-(3,3-difluoro-piperidin-4-yl)amine 14, 0.81 g (5.4 mmol; 1 equiv) of sodium iodide, 2.73 g (27.0 mmol; 5 equiv) of triethylamine and 1.05 g (5.4 mmol; 1 equiv) of 1-(3-chloropropoxy)-4-fluorobenzene in 70 mL was stirred at 120° C. during 30 hours. Another portion of 2.73 g (27.0 mmol; 5 equiv) of triethylamine was added and the mixture stirred at 120° C. during 16 hours. Then 1.05 g (5.4 mmol; 1 equiv) of 1-(3-chloropropoxy)-4-fluorobenzene was added and the mixture was stirred at 120° C. during 54 hours until the reaction was completed. The solvent was removed under vacuum and the crude oil was redissolved in 100 mL of EtOAc and washed with brine and dried over MgSO4. Filtration of the solids and evaporation of the solvent resulted in a crude oil which was purified via flash chromatography (hexane/EtOAc 1:1, Rf=0.19-0.38) yielding 1.00 g (2.6 mmol; 49% yield) of benzyl-{3,3-difluoro-1-[3-(4-fluoro-phenoxy)propyl]piperidin-4-yl}amine 15 as a brown oil.

Workup

  1. stirringthe mixture stirred at 120° C. during 16 hours
  2. stirringthe mixture was stirred at 120° C. during 54 hours until the reaction
  3. customThe solvent was removed under vacuum
  4. dissolutionthe crude oil was redissolved in 100 mL of EtOAc
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationFiltration of the solids and evaporation of the solvent
  8. customresulted in a crude oil which
  9. customwas purified via flash chromatography (hexane/EtOAc 1:1, Rf=0.19-0.38)

Sources & evidence

ORD record
ord-450ce298f97c4c699882cfc895fcbb7d
Source dataset
uspto-grants-2015_09
Patent number
US09139523B2

Reaction notes

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