Toluene → HCID 67003971, compound

HRID 2095621Notes

Reaction equation

HRID 2095621 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:14]3[C:19]([O:20][CH2:21][CH3:22])=[CH:18][CH:17]=[C:16]([F:23])[C:15]=3[Cl:24])OC)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.B(F)(F)F.[CH3:29]COCC.C[Zn]C.C1(C)C=CC=CC=1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:14]3[C:19]([O:20][CH2:21][CH3:22])=[CH:18][CH:17]=[C:16]([F:23])[C:15]=3[Cl:24])[CH3:29])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8000Boron trifluoride etherateHCID 67004450HCID 67004450, compoundHCID 178477796HCID 178477796, compound

Product 1

HCID 67003971HCID 67003971, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cold (−78° C.) solution of 5-Bromo-3-[(2-chloro-6-ethoxy-3-fluorophenyl)-methoxymethyl]-1H-pyrrolo[2,3-b]pyridine (3.0 g, 7.2 mmol) in THF (30 mL) was added BF3.OEt2 (7.1 mL, 56.3 mmol). The reaction mixture was stirred for 1 h, and 2M solution of dimethylzinc in toluene (28 mL, 56 mmol) was added dropwise. The reaction mixture was stirred for 12 h at 50° C. and was quenched with saturate aq. ammonium chloride. The organic layer was separated and aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated to give a yellowish residue. The residue was adsorbed on silica and purified (100% DCM→5% methanol/DCM) by small pad of silica. The resulting solid was recrystallized with diisopropyl ether to give the title compound. 1H NMR (CDCl3, 400 MHz): δ=1.25 (t, 3H, J=7.0 Hz), 1.79 (d, 3H, J=7.0 Hz), 3.74 (bs, 1H), 3.96 (q, 1H, J=7.0 Hz), 5.05 (q, 1H, J=7.0 Hz), 6.66-6.69 (m, 1H), 6.97 (t, 1H, J=9.0 Hz), 7.69 (s, 1H), 8.25 (s, 1H), 9.24 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred for 12 h at 50° C.
  2. customwas quenched with saturate aq. ammonium chloride
  3. customThe organic layer was separated
  4. extractionaqueous layer was extracted with ethyl acetate (2×30 mL)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto give a yellowish residue
  9. custompurified (100% DCM→5% methanol/DCM) by small pad of silica
  10. customThe resulting solid was recrystallized with diisopropyl ether

Sources & evidence

ORD record
ord-e4400956715e40ff99d5442bd78aec67
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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