Sodium Carbonate → (2R)-2-methyl-1-{2-[5-(2-methylphenyl)-1-benzofuran-2-yl]ethyl}pyrrolidine

HRID 494859Notes

Reaction equation

HRID 494859 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH2:10][CH2:11][N:12]3[CH2:16][CH2:15][CH2:14][C@H:13]3[CH3:17])=[CH:7][C:6]=2[CH:18]=1.[CH3:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC=CC=1.C(O)C.CO.CS(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:17][C@@H:13]1[CH2:14][CH2:15][CH2:16][N:12]1[CH2:11][CH2:10][C:8]1[O:9][C:5]2[CH:4]=[CH:3][C:2]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH3:19])=[CH:18][C:6]=2[CH:7]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 11220543(2R)-1-[2-(5-bromo-1-benzofuran-2-yl)ethyl]-2-methylpyrrolidine

Product 1

HCID 67534397(2R)-2-methyl-1-{2-[5-(2-methylphenyl)-1-benzofuran-2-yl]ethyl}pyrrolidine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 702EthanolSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Conditions

Temperature
75 °C

Procedure

A portion (˜330 μL) of a solution of the product from Example 115A (650 mg, 2.1 mmol) and tetrakis(triphenylphosphine)palladium (125 mg, 0.11 mmol) in benzene (6.2 mL) was added to a mixture of (2-methylphenyl)boronic acid (˜24 mg, ˜0.18 mmol) in ethanol (150 μL). The mixture was treated with 2.0 M aqueous Na2CO3 (200 μL, 0.4 mmol), and the reaction vial was sealed, placed on a heater-stirrer apparatus, and heated at 75° C. for four days. The mixture was cooled to room temperature, diluted with 1:1 MeOH/DMSO (1 mL), filtered, and purified by HPLC [Waters Nova-Pak HR C18 column (25 mm×100 mm, 6 μm particle size) using a gradient of 10% to 100% MeCN/0.1% aqueous TFA over 8 min (10 min run time) at a flow rate of 40 mL/min.] to provide the title compound. MS (APCI) m/z 320 (M+H)+.

Workup

  1. customthe reaction
  2. customvial was sealed
  3. customplaced on a heater-stirrer
  4. temperatureThe mixture was cooled to room temperature
  5. filtrationfiltered
  6. custompurified by HPLC [Waters Nova-Pak HR C18 column (25 mm×100 mm, 6 μm particle size)
  7. customover 8 min
  8. custom(10 min run time)

Sources & evidence

ORD record
ord-f0cec3a5950d42a28876a77a61b32539
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

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