Dichloromethane → Methyl [4-bromo-2-(4-propoxyphenyl)thien-3-yl]acetate

HRID 2373702Notes

Reaction equation

HRID 2373702 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([Br:12])[C:6]=1[CH2:7][C:8]([O:10][CH3:11])=[O:9].[CH2:13]([O:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1)[CH2:14][CH3:15].C([O-])([O-])=O.[K+].[K+].ClCCl>O.CCOC(C)=O.CCCCCC.O1CCOCC1>[Br:12][C:5]1[C:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])=[C:2]([C:20]2[CH:21]=[CH:22][C:17]([O:16][CH2:13][CH2:14][CH3:15])=[CH:18][CH:19]=2)[S:3][CH:4]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 44564904-Propoxyphenylboronic AcidHCID 86607173Methyl (2,4-dibromothien-3-yl)acetate

Product 1

HCID 86607172Methyl [4-bromo-2-(4-propoxyphenyl)thien-3-yl]acetateYield 57.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Into dioxane (3 mL) was dissolved methyl (2,4-dibromothien-3-yl)acetate (0.355 g, 1.13 mmol) and 4-propoxyphenylboronic acid (0.214 g, 1.19 mmol). K2CO3 (0.195 g, 1.41 mmol) was dissolved in H2O (0.4 mL) and added to the dioxane. The solution was degassed by bubbling argon through the mixture for five minutes. {1,1′-Bis(diphenylphosphino)-ferrocene}dichloropalladium(II) complex with dichloromethane (1:1) (0.027 g, 0.033 mmol) was added and the mixture heated under argon to 50° C. for 4 hours (followed by TLC 15:1 Hexane:EtOAc). The solvents were removed and the mixture partitioned between EtOAc and H2O. The EtOAc layer was dried (MgSO4) and absorbed onto silica gel. The product was purified by flash chromatography (25:1 hexane:EtOAc) to yield methyl [4-bromo-2-(4-propoxyphenyl)thien-3-yl]acetate (0.240 g) as a clear oil. 1H NMR (500 MHz, DMSO-d6) δ: 0.99 (t, 3H, J=7.32 Hz), 1.75 (m, 2H), 3.65 (s, 5H), 3.98 (t, 2H, J=6.6 Hz), 7.05 (d, 2H, J=8.2 Hz), 7.33 (d, 2H, J=8.2 Hz), 7.72 (s, 1H). MS (ES) m/z 369.0 ([M+H]+). MS (ES) m/z 386.0 ([M+NH4]+).

Workup

  1. customThe solution was degassed
  2. customby bubbling argon through the mixture for five minutes
  3. customThe solvents were removed
  4. customthe mixture partitioned between EtOAc and H2O
  5. dry with materialThe EtOAc layer was dried (MgSO4)
  6. customabsorbed onto silica gel
  7. customThe product was purified by flash chromatography (25:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-b620c22040d74cdd992425de555f8416
Source dataset
uspto-grants-2008_12
Patent number
US07459567B2

Reaction notes

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