Sodium Carbonate → 6-Methoxy-2-[4-(2-(1-pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophene

HRID 1386967Notes

Reaction equation

HRID 1386967 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[C:9](B(O)O)[S:8][C:7]=2[CH:14]=1.Br[C:16]1[CH:29]=[CH:28][C:19]([O:20][CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:18][CH:17]=1.[Al].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1.[Cl-].[Na+].O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[C:9]([C:16]3[CH:17]=[CH:18][C:19]([O:20][CH2:21][CH2:22][N:23]4[CH2:24][CH2:25][CH2:26][CH2:27]4)=[CH:28][CH:29]=3)[S:8][C:7]=2[CH:14]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 70657N-(2-(p-bromophenoxy)ethyl)pyrrolidineHCID 5359268AluminumHCID 10560276(6-Methoxy-1-benzothiophen-2-yl)boronic acid

Product 1

HCID 106894206-Methoxy-2-[4-(2-(1-pyrrolidinyl)ethoxy)phenyl]benzo[b]thiopheneYield 55%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 241BenzeneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

To a slurry of 6-methoxybenzo[b]thiophene-2-boronic acid (Example 1, Part A) (6.43 g, 30.9 mmol) in 310 mL of benzene was added 1-(2-(4-bromophenoxy)ethyl)pyrrolidine (5.80 mL, 28.1 mmol). Upon addition the reaction mixture turned to a yellow homogeneous solution. The reaction flask was then covered with aluminum foil to keep out light. To this was added 1.07 g (0.92 mmol) of tetrakis(triphenylphosphine)-palladium(0), followed by 30 mL of 2.0 N sodium carbonate solution. The biphasic mixture was heated at 85° C. for 3 h with vigorous stirring. The mixture was cooled to 0° C. and 175 mL of brine solution was added. The layers were separated and the aqueous layer was extracted with 1.0 L of EtOAc. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by PrepLC (53:35:2 THF-hexanes-TEA) to afford 5.42 g (15.3 mmol, 55%) of an off-white solid.

Workup

  1. additionUpon addition the reaction mixture
  2. temperatureThe mixture was cooled to 0° C.
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with 1.0 L of EtOAc
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by PrepLC (53:35:2 THF-hexanes-TEA)

Sources & evidence

ORD record
ord-c690506a40d74a129630e643d9dbf4e0
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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