(Diethylamino)sulfur trifluoride → 4-Benzyl-2-(fluoromethyl)-1-methylpiperazine

HRID 1919156Notes

Reaction equation

HRID 1919156 reaction equation
C(N(S(F)(F)[F:7])CC)C.[CH2:10]([N:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH:19]([CH2:24]O)[CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[CH2:10]([N:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH:19]([CH2:24][F:7])[CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 19777247(4-Benzyl-1-methylpiperazin-2-yl)methanol

Product 1

HCID 197772584-Benzyl-2-(fluoromethyl)-1-methylpiperazineYield 33%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of diethylaminosulfur trifluoride (10.8 mL, 81.8 mmol) in methylene chloride under N2 was added 336b (9.0 g, 40.9 mmol) in methylene chloride dropwise. The yellow solution was stirred at 0° C. for 1 h and then room temperature for 15 h. The reaction mixture was then diluted with NaHCO3, and the organic layer was separated and dried over Na2SO4. The crude product was purified on silica gel column chromatography eluting with 50:1 methylene chloride/methanol to afford 336c as a yellow oil (3.0 g, 33%). MS: [M+H]+ 223. 1H NMR (500 MHz, DMSO) δ 7.28 (m, 5H), 4.50 (m, 0.5H), 4.43 (m, 1H), 4.35 (m, 0.5H), 3.45 (s, 2H), 2.67 (m, 2H), 2.60 (m, 1H), 2.29 (m, 1H), 2.24 (s, 3H), 2.20 (m, 1H), 2.11 (m, 1H), 1.94 (m, 1H).

Workup

  1. waitroom temperature for 15 h
  2. customthe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. customThe crude product was purified on silica gel column chromatography
  5. washeluting with 50:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-dfc7a3eee4e448d285453266cc6cb290
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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