Acetate → (+/-)-[9-[(4-CHLOROPHENYL)THIO]-6-FLUORO-8-(2-METHYLPHENYL)-2,3-DIHYDRO-1H-PYRROLO[1,2-a]INDOL-1-YL]ACETIC ACID

HRID 857409Notes

Reaction equation

HRID 857409 reaction equation
C[CH:2]([CH:6]1[C:10]2=[C:11]([S:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:12]3[C:13](Br)=[CH:14][C:15]([F:18])=[CH:16][C:17]=3[N:9]2[CH2:8][CH2:7]1)[C:3]([O-:5])=[O:4].[CH3:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1B(O)O.C([O-])(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(O)CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([S:20][C:11]2[C:12]3[C:13]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[CH3:28])=[CH:14][C:15]([F:18])=[CH:16][C:17]=3[N:9]3[CH2:8][CH2:7][CH:6]([CH2:2][C:3]([OH:5])=[O:4])[C:10]=23)=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 175AcetateHCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 21867555(+)-methyl{8-bromo-9-[(4-chlorophenyl)thio]-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl}acetate

Product 1

HCID 10298594(+/-)-[9-[(4-CHLOROPHENYL)THIO]-6-FLUORO-8-(2-METHYLPHENYL)-2,3-DIHYDRO-1H-PYRROLO[1,2-a]INDOL-1-YL]ACETIC ACIDYield 92%

Reagents, catalysts & solvents 2

HCID 15220664Palladium--triphenylphosphane (1/1)CatalystHCID 10311-PropanolSolvent

Conditions

Temperature
80 °C

Procedure

To (+/−)-methyl[8-bromo-9-[(4-chlorophenyl)sulfanyl]-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl]acetate (Example 7, Step 9, 100 mg, 0.21 mmol) in 1-propanol (2 mL) were added 2-methylphenylboronic acid (57 mg, 0.42 mmol), 3:1 mixture of triphenylphosphine/palladium (>) acetate (11 mg) and 2M aqueous potassium carbonate (0.3 mL). The mixture was degassed and stirred at 80° C. for 6 h and the reaction mixture was cooled to r.t. Then THF (3 mL) and 1N LiOH were added and the mixture was stirred for 2 h at r.t. AcOH (0.5 mL) and brine were added and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 40% EtOAc/hexane containing 1% AcOH to give 90 mg of the title compound.

Workup

  1. customThe mixture was degassed
  2. temperaturethe reaction mixture was cooled to r.t
  3. additionThen THF (3 mL) and 1N LiOH were added
  4. stirringthe mixture was stirred for 2 h at r.t
  5. additionAcOH (0.5 mL) and brine were added
  6. extractionthe aqueous layer was extracted with EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluted with 40% EtOAc/hexane containing 1% AcOH

Sources & evidence

ORD record
ord-85dd169599e140d1b547256cdc85ecdd
Source dataset
uspto-grants-2006_12
Patent number
US07144913B2

Reaction notes

Loading…