Dimethylformamide → 7-Bromo-9,9-diethylfluorene-2-carboxaldehyde

HRID 341115Notes

Reaction equation

HRID 341115 reaction equation
[CH2:1]([C:3]1([CH2:18][CH3:19])[C:15]2[CH:14]=[C:13]([Br:16])[CH:12]=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][C:6](Br)=[CH:7][CH:8]=2)[CH3:2].C([Li])CCC.CN([CH:28]=[O:29])C>C1COCC1.C(=O)=O.C(O)C.Cl.C1(C)C=CC=CC=1>[Br:16][C:13]1[CH:14]=[C:15]2[C:10]([C:9]3[CH:8]=[CH:7][C:6]([CH:28]=[O:29])=[CH:5][C:4]=3[C:3]2([CH2:1][CH3:2])[CH2:18][CH3:19])=[CH:11][CH:12]=1

Participants

8

Reactant 3

HCID 6228DimethylformamideHCID 35310452,7-Dibromo-9,9-diethylfluoreneHCID 178418339Butyllithium

Product 1

HCID 154763497-Bromo-9,9-diethylfluorene-2-carboxaldehydeYield 78.4%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 19604758Methanedione--ethanol (1/1)Solvent

Conditions

Temperature
5 °C

Procedure

To a mechanically stirred solution of 9,9-diethyl-2,7-dibromofluorene (59.38 g, 0.1563 mol), in THF (325 mL), cooled in dry ice-ethanol bath, n-butyllithium (104 mL of 1.6 M solution in hexanes, 0.1664 mol, 1.06 eq) was added dropwise over 25 min. After 20 min, DMF (17 mL, 0.22 mol) in THF (30 mL) was added, and the mixture was stirred in the cooling bath for 1.5 hr, and outside the bath for 1 hr. The reaction was then cooled to 5° C., and treated with hydrochloric acid (12.5 of concentrated hydrochloric acid diluted with 50 mL water). The mixture was diluted with 200 mL of toluene, and the aqueous phase was separated and extracted with 200 mL of toluene. The combined organic phase was washed with dilute sodium bicarbonate solution, dried over magnesium sulfate, and concentrated. The residual solids were recrystallized from heptane-ethyl acetate (9:1), to get colorless solids, 40.29 g (78.4% yield) m.p. 126-128° C. The mother liquor after chromatography over 150 g silica gel, elution with 1:1 heptane-toluene, and trituration of residual solids in hexanes gave additional product, 6.56 g (12.8% yield, total 91% yield), m.p. 126-128° C. Mass Spec: m/z 328, 330, (M+). A sample for analysis was prepared by recrystallization from hexanes, m.p. 127-129° C. Analysis: Calculated for C18H17BrO, C, 65.55, H, 5.20, and Br 24.27%. Found, C, 65.60, H, 5.51, and Br 24.71%.

Workup

  1. waitoutside the bath for 1 hr
  2. customthe aqueous phase was separated
  3. extractionextracted with 200 mL of toluene
  4. washThe combined organic phase was washed with dilute sodium bicarbonate solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residual solids were recrystallized from heptane-ethyl acetate (9:1)
  8. customto get colorless solids, 40.29 g (78.4% yield) m.p. 126-128° C
  9. washThe mother liquor after chromatography over 150 g silica gel, elution with 1:1 heptane-toluene, and trituration of residual solids in hexanes
  10. customgave additional product, 6.56 g (12.8% yield, total 91% yield), m.p. 126-128° C

Sources & evidence

ORD record
ord-4162ffb309d7412c9c7429f4dbc5cff2
Source dataset
uspto-grants-2014_11
Patent number
US08895730B2

Reaction notes

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