Boron trifluoride etherate → HCID 178459004, compound

HRID 1711261Notes

Reaction equation

HRID 1711261 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=2)[CH:3]=1.C([Mg]Cl)(C)C.[CH3:29][C:30]1([CH3:33])[CH2:32][O:31]1.B(F)(F)F.CCOCC.[Li]C(C)(C)C>C1COCC1>[C:18]1([C:4]2[CH:3]=[C:2]([CH2:29][C:30]([OH:31])([CH3:33])[CH3:32])[CH:7]=[CH:6][C:5]=2[NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=1

Participants

7

Reactant 5

HCID 8000Boron trifluoride etherateHCID 11208Isobutylene oxideHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compoundHCID 178510376HCID 178510376, compound

Product 1

HCID 178459004HCID 178459004, compoundYield 15.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-cyano-1H-imidazole-2-carboxylic acid (4-bromo-2-cyclohex-1-enyl-phenyl)-amide (prepared in Example 11, step (g)) (0.10 g, 0.27 mmol) in 1.5 mL of THF at −40° C. was added 0.15 mL of i-PrMgCl (0.30 mmol, 2 M solution in THF) and the solution was stirred at this temperature for 15 min. The mixture was then cooled to −78° C. and 2,2-dimethyl-oxirane (0.12 mL, 1.3 mmol) was added followed by boron trifluoride etherate (0.044 mL, 0.35 mmol) and t-BuLi (0.41 mL, 0.69 mmol, 1.7 M solution in pentane). After stirring for 30 min at −78° C. the mixture was quenched with satd NH4Cl (10 mL), extracted with EtOAc (2×10 mL) and the organic layer was dried over Na2SO4 and concentrated. The title compound was eluted from a 20-g SPE column with 50% EtOAc/hexanes to give 0.015 g (15%) of a white solid: 1H-NMR (DMSO-d6, 400 MHz): δ 14.25 (s, 1H), 9.71 (s, 1H), 8.33 (s, 1H), 7.84 (d, J=8.2 Hz, 1H), 7.14 (dd, J=8.2, 1.9 Hz, 1H), 7.06 (d, J=1.9 Hz, 1H), 5.74 (s, 1H), 4.63 (t, J=5.2 Hz, 1H), 3.61 (m, 2H), 2.70 (t, J=7.0 Hz, 2H), 2.23-2.11 (m, 4H), 1.76-1.62 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C21H24N4O2, 365.2 (M+H), found 365.1.

Workup

  1. stirringAfter stirring for 30 min at −78° C. the mixture
  2. customwas quenched with satd NH4Cl (10 mL)
  3. extractionextracted with EtOAc (2×10 mL)
  4. dry with materialthe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. washThe title compound was eluted from a 20-g SPE column with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-2c91cb621e6d4b4981dd5e742c30e587
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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