Hydrochloric Acid → HCID 58189127, compound

HRID 1423091Notes

Reaction equation

HRID 1423091 reaction equation
I[CH2:2]I.[Br:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH:14]=[CH2:15])[CH:6]=1.Cl>C(Cl)Cl>[Br:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH:14]2[CH2:2][CH2:15]2)[CH:6]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6346DiiodomethaneHCID 66602974HCID 66602974, compound

Product 1

HCID 58189127HCID 58189127, compoundYield 69.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

Into a 25 mL flame-dried flask were added diethylzinc (8.75 mL, 1 N solution in hexanes). The solution was cooled to −20° C. and a solution of trichloroacetic acid (1.43 g, 8.75 mmol, dissolved in 2 mL of CH2Cl2 was added dropwise over 10 min, then the solution was stirred an additional 20 min. A solution of diiodomethane (2.38 g, 8.89 mmol) in 1 mL CH2Cl2 was then added dropwise and the solution was stirred an additional 20 minutes. A solution of 4-bromo-1-methoxy-2-vinyloxy-benzene (1.029 g, 4.365 mmol, dissolved in 900 uL CH2Cl2) was then added and the reaction mixture was stirred for 8 h at room temperature. The reaction mixture was poured onto a 100 mL 1 N aqueous HCl solution containing some ice, then extracted 3× with EtOAc. The combined organic phase was washed with 1 N aqueous NaHCO3, brine, then dried (MgSO4), filtered and concentrated. Purification by flash column on silica gel (0-100% Hexanes/EtOAc gradient) to afford titled compound as a colorless crystalline solid (738 mg, 67%). 1H NMR (DMSO-d6) 7.33 (s, 1H), 7.06 (d, J=8.4, 1H), 6.90 (d, J=8.4, 1H), 3.84 (m, 1H), 3.70 (s, 3H), 0.75 (m, 2H), 0.64 (m, 2H). LC/MS (Method B) 3.64 min, [M+1]+ 243/245.

Workup

  1. customInto a 25 mL flame-dried flask
  2. additionwere added diethylzinc (8.75 mL, 1 N solution in hexanes)
  3. dissolutiona solution of trichloroacetic acid (1.43 g, 8.75 mmol, dissolved in 2 mL of CH2Cl2
  4. additionwas added dropwise over 10 min
  5. stirringthe solution was stirred an additional 20 minutes
  6. stirringthe reaction mixture was stirred for 8 h at room temperature
  7. additioncontaining some ice
  8. extractionextracted 3× with EtOAc
  9. washThe combined organic phase was washed with 1 N aqueous NaHCO3, brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash column on silica gel (0-100% Hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-bb74c70ac87e404db261d7c05b9e685e
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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