Water → methyl 2-[2-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-indol-3-yl]pentanoate

HRID 591000Notes

Reaction equation

HRID 591000 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].O.CC1(C)C(C)(C)OB([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[O:22][CH2:21][CH2:20][CH2:19]3)O1.Br[C:28]1[N:29]([CH3:45])[C:30]2[C:35]([C:36]=1[CH:37]([CH2:42][CH2:43][CH3:44])[C:38]([O:40][CH3:41])=[O:39])=[CH:34][CH:33]=[CH:32][CH:31]=2>CN(C)C=O.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.[Pd]>[O:22]1[C:23]2[CH:24]=[CH:25][C:16]([C:28]3[N:29]([CH3:45])[C:30]4[C:35]([C:36]=3[CH:37]([CH2:42][CH2:43][CH3:44])[C:38]([O:40][CH3:41])=[O:39])=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:17][C:18]=2[CH2:19][CH2:20][CH2:21]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 438110342-(3,4-dihydro-2H-1-benzopyran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 70819053methyl 2-(2-bromo-1-methyl-1H-indol-3-yl)pentanoate

Product 1

HCID 70855400methyl 2-[2-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-indol-3-yl]pentanoateYield 86%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Under a nitrogen atmosphere, sodium carbonate (370 mg, 3.5 mmol), water (20 mL), palladium tetrakis(triphenylphosphine) (620 mg, 0.54 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (904 mg, 3.48 mmol) were added to a solution of methyl 2-(2-bromo-1-methyl-1H-indol-3-yl)pentanoate (1.13 g, 3.4 mmol) in N,N-dimethylformamide (80 mL). The mixture was heated at 110° C. for 2 hours, concentrated in vacuo and water (40 mL) was added. The aqueous layer was extracted with ethyl acetate (2×20 mL). The organic layer was washed with brine (20 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 95/5) to afford the desired product (12d) as a white solid (1.1 g, 2.91 mmol, 86%).

Workup

  1. concentrationconcentrated in vacuo and water (40 mL)
  2. additionwas added
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  4. washThe organic layer was washed with brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 95/5)

Sources & evidence

ORD record
ord-8fb792da203b4b21b3270f8714fef202
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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