Diethyl Ether → HCID 71145589, compound

HRID 535321Notes

Reaction equation

HRID 535321 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.CC[Mg+].[Br-].C(OCC)C.[CH:18]([CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:22][CH2:21]1)=[O:19]>C1COCC1>[CH2:29]([O:28][C:26]([N:23]1[CH2:24][CH2:25][CH:20]([CH:18]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)[OH:19])[CH2:21][CH2:22]1)=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 115221-Bromo-4-iodobenzene2×HCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 178461630HCID 178461630, compound

Product 1

HCID 71145589HCID 71145589, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-bromo-4-iodobenzene (17.16 g, 60.7 mmol) in THF (130 ml) was immersed in a dry ice-methanol bath. EtMgBr 3M in diethylether (27.0 ml, 81 mmol) was added slowly via syringe at −44° C. to −40° C. (exothermic reaction, grey precipitation!). The reaction mixture was allowed to warm up to −10° C. and after 2 hrs 1-bromo-4-iodobenzene was gone. Then a solution of benzyl 4-formylpiperidine-1-carboxylate (10 g, 40.4 mmol) in THF (30 ml) was added slowly below −65° C. The reaction was allowed to warm up to room temperature and stirred for 14 hrs. The reaction mixture was quenched with saturated aqueous ammonia chloride solution and diluted with ethyl acetate. The organic phase was separated and washed with brine. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude material which was purified by automated column chromatography (normal phase, ethyl acetate/n-heptane) to obtain the title compound as colorless oil.

Workup

  1. custom(exothermic reaction, grey precipitation!)
  2. customThe reaction mixture was quenched with saturated aqueous ammonia chloride solution
  3. additiondiluted with ethyl acetate
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto obtain the crude material which
  10. customwas purified by automated column chromatography (normal phase, ethyl acetate/n-heptane)

Sources & evidence

ORD record
ord-7dc808dcb1e2459caf2422e1401a83b5
Source dataset
uspto-grants-2014_10
Patent number
US08859535B2

Reaction notes

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