tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-((6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate

HRID 1621394Notes

Reaction equation

HRID 1621394 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([F:22])=[N:20][CH:21]=1>CN(C)C=O>[F:22][C:19]1[N:20]=[CH:21][C:16]([CH2:15][N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 220506385-(Bromomethyl)-2-fluoropyridine

Product 1

HCID 59548414Tert-butyl 4-((6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylateYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl piperazine-1-carboxylate (Aldrich, St. Louis, Mo., 17.77 g, 95 mmol) was added to a stirred solution of 5-(bromomethyl)-2-fluoropyridine (15.11 g, 80 mmol) in N,N-dimethylformamide (120 mL) at 0° C. and the suspension was stirred at room temperature overnight. The resulting thick reaction mixture was quenched with cold water (50 mL), the resulting suspension was stirred for 30 min, and the resulting solid was collected and washed with additional cold water (50 mL). The off-white precipitate was dried under vacuum to give the title compound tert-butyl 4-((6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate (19.7494 g, 66.9 mmol, 84% yield) as a white solid. LCMS (API-ES) m/z 296 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 8.13 (s, 1H) 7.90 (td, J=8.02, 1.37 Hz, 1H) 7.15 (dd, J=8.31, 2.05 Hz, 1H) 3.51 (s, 2H) 3.30 (br. s., 4H) 2.10-2.40 (m, 4H) 1.39 (s, 9H).

Workup

  1. customThe resulting thick reaction mixture was quenched with cold water (50 mL)
  2. stirringthe resulting suspension was stirred for 30 min
  3. customthe resulting solid was collected
  4. washwashed with additional cold water (50 mL)
  5. customThe off-white precipitate was dried under vacuum

Sources & evidence

ORD record
ord-f104651cec0d443f83b64473a1b48cc8
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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