Methyl iodide → 4-Benzyl-1-tert-butoxycarbonyl-2(S)-(2-methoxyethyl)piperazine

HRID 1598448Notes

Reaction equation

HRID 1598448 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@@H:10]([CH2:21][CH2:22][OH:23])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24]I>>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[C@@H:10]([CH2:21][CH2:22][O:23][CH3:24])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 6328Methyl iodideHCID 15406045(S)-4-Benzyl-2-(2-hydroxyethyl)piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 154060464-Benzyl-1-tert-butoxycarbonyl-2(S)-(2-methoxyethyl)piperazineYield 83.7%

Conditions

Temperature
0 °C

Procedure

A solution of 4-benzyl-1-tert-butoxycarbonyl-2(S)-(2-hydroxyethyl)piperazine (0.322 g, 1.00 mmol) in dry, degassed dimethylformamide (4 mL) was cooled under nitrogen to 0° C. Sodium hydride was added (0.052 g, 60% dispersion in oil, 1.30 mmol) followed by methyl iodide (0.88 mL, 1.41 mmol). After 3 h, the reaction was quenched with saturated ammonium chloride. The solvent was removed in vacuo and the residue partitioned between ethyl acetate and saturated sodium bicarbonate. The ethyl acetate was washed with water, saturated sodium chloride solution, and dried over magnesium sulfate. The crude product was chromatographed on silica gel with 40% ethyl acetate in hexane to obtain the title compound as a clear oil (280 mg). NMR (CD3OD, 300 MHz) δ 7.3 (5H, m), 4.19 (1H, m), 3.85 (1H, dm, J=13 Hz), 3.56 (1H, d, J=13 Hz), 3.16 (1H, d, J=13 Hz), 3.28 (2H, m, partially obscured by solvent), 3.23 (3H, s), 3.08 (1H, t, J=13 Hz), 2.80 (1H, d, J=11 Hz), 2.70 (1H, d, J=11 Hz), 2.03 (3H, m), 1.86, (1H, sextet, J=6 Hz), 1.45 (9H, s).

Workup

  1. customdegassed dimethylformamide (4 mL)
  2. additionSodium hydride was added (0.052 g, 60% dispersion in oil, 1.30 mmol)
  3. customthe reaction was quenched with saturated ammonium chloride
  4. customThe solvent was removed in vacuo
  5. customthe residue partitioned between ethyl acetate and saturated sodium bicarbonate
  6. washThe ethyl acetate was washed with water, saturated sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. customThe crude product was chromatographed on silica gel with 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-8880fdc02ce0452391ba7ebbed1eeb5d
Source dataset
uspto-grants-1998_04
Patent number
US05736539

Reaction notes

Loading…