Hexane → HCID 178451675, compound

HRID 716535

Reaction equation

HRID 716535 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([Br:19])=[C:16](Br)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.CCCCCC>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:17][CH:16]=[C:15]([Br:19])[N:14]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8058HexaneHCID 53429454Tert-butyl 2-(4,5-dibromo-1H-imidazol-2-YL)pyrrolidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 178451675HCID 178451675, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

To a solution of intermediate 47 (75.93 mmol) in dry tetrahydrofuran (300 mL) at −78° C. under nitrogen was added n-butyllithium 2.5M solution in hexane (275 mmol). After completion of addition, the mixture was stirred under nitrogen between −70° C. and −80° C. for 30 min, and then allowed to warm up to −60° C. The reaction was carefully quenched with methanol (20 mL), maintaining the temperature below −40° C. The reaction mixture was then allowed to reach to 0° C., and water (100 mL) and ethyl acetate (100 mL) were added. The layers were separated and the organic was washed sequentially with a diluted HCl solution and brine. After evaporation in vacuo of the organic layer, the residue was purified by silica gel chromatography (eluent: DCM to DCM/methanol (1%)) to give compound 48 as a white foam in 52% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.16-1.37 (2s, 9H), 1.78-1.94 (m, 3H), 2.08-2.21 (m, 1H), 3.26-3.34 (m, 1H), 3.42-3.50 (m, 1H), 4.63-4.74 (m, 1H), 7.07-7.10 (m, 1H), 12.09-12.13 (m, 1H); MS (ESI, EI+) m/z=316.23-318.24 (MH+).

Workup

  1. additionAfter completion of addition
  2. customThe reaction was carefully quenched with methanol (20 mL)
  3. temperaturemaintaining the temperature below −40° C
  4. customto reach to 0° C.
  5. additionwater (100 mL) and ethyl acetate (100 mL) were added
  6. customThe layers were separated
  7. washthe organic was washed sequentially with a diluted HCl solution and brine
  8. customAfter evaporation in vacuo of the organic layer
  9. customthe residue was purified by silica gel chromatography (eluent: DCM to DCM/methanol (1%))

Sources & evidence

ORD record
ord-533e92fdf7594eb9a330b8b8dd6e02aa
Source dataset
uspto-grants-2015_11
Patent number
US09187496B2

Linked notes

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