Sodium Iodide → N-tert-butyl-3-(piperazin-1-ylmethyl)benzamide

HRID 1878329Notes

Reaction equation

HRID 1878329 reaction equation
[C:1]([NH:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13]Cl)[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[N:16]1(C(OC(C)(C)C)=O)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.[I-].[Na+].C(N(CC)CC)C.FC(F)(F)C(O)=O>O1CCCC1>[C:1]([NH:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 43156221N-tert-butyl-3-(chloromethyl)benzamide

Product 1

HCID 66877987N-tert-butyl-3-(piperazin-1-ylmethyl)benzamideYield 71.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

N-tert-Butyl-3-(chloromethyl)benzamide (14.71 g, 65.2 mmol), tert-butyl piperazine-1-carboxylate (12.14 g, 65.2 mmol), sodium iodide (1.95 g, 13.0 mmol), triethylamine (27.3 mL, 195.5 mmol) and tetrahydrofuran (125 mL) were stirred together at room temperature for 18 hours. The reaction was then concentrated under vacuum and the residue dissolved in ethyl acetate. The organic mixture was washed consecutively with saturated aqueous sodium hydrogen carbonate solution, water (×2) and brine then concentrated under vacuum. The residue was dissolved in dichloromethane (100 mL), treated with trifluoroacetic acid (25.0 mL, 326.0 mmol) and stirred at 60° C. for 2.5 hours. The reaction was concentrated under vacuum and purified by strong cation exchange (SCX) chromatography, eluting macroporous polystyrene sulfonic acid with 2M ammonia in methanol. The resulting solution was concentrated under vacuum to give the title compound (12.8 g) as a white solid.

Workup

  1. concentrationThe reaction was then concentrated under vacuum
  2. dissolutionthe residue dissolved in ethyl acetate
  3. washThe organic mixture was washed consecutively with saturated aqueous sodium hydrogen carbonate solution, water (×2) and brine
  4. concentrationthen concentrated under vacuum
  5. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  6. concentrationThe reaction was concentrated under vacuum
  7. custompurified by strong cation exchange (SCX) chromatography
  8. washeluting macroporous polystyrene sulfonic acid with 2M ammonia in methanol
  9. concentrationThe resulting solution was concentrated under vacuum

Sources & evidence

ORD record
ord-24436310e3f64e94903a64df958703ba
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

Loading…