Imidazole → HCID 58181004, compound

HRID 1772827Notes

Reaction equation

HRID 1772827 reaction equation
[OH:1][CH2:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.N1C=CN=C1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]>CN(C=O)C>[Si:21]([O:1][CH2:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 223865084-N-Boc-2-hydroxymethylpiperazine

Product 1

HCID 58181004HCID 58181004, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of racemic tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (1.5 g, 6.9 mmol, AstaTech) and 1H-imidazole (1.4 g, 21 mmol) in DMF (20 mL) cooled to 0° C. was added tert-butyldimethylsilyl chloride (2.1 g, 14 mmol). The mixture was then allowed to reach RT and stir for 20 h. The mixture was quenched by the addition of saturated ammonium chloride. The product was extracted with two portions of ethyl acetate. The organic extract was washed with water, brine, dried over sodium sulfate and concentrated to afford a clear oil. Flash chromatography on a 120 g silica gel cartridge, eluting with a slow gradient from 0-6% MeOH in DCM afforded purified product (1.15 g, 50%). 1H NMR (400 MHz, CDCl3): δ 4.00-1.63 (m, 9H), 1.45 (s, 9H), 0.89 (s, 9H), 0.05 (s, 6H); LCMS (M+H)+: 331.2.

Workup

  1. customto reach RT
  2. customThe mixture was quenched by the addition of saturated ammonium chloride
  3. extractionThe product was extracted with two portions of ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto afford a clear oil
  9. washFlash chromatography on a 120 g silica gel cartridge, eluting with a slow gradient from 0-6% MeOH in DCM
  10. customafforded
  11. custompurified product (1.15 g, 50%)

Sources & evidence

ORD record
ord-45137383afb74f9e87e46ffe1296d408
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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