Ethyl Acetate → HCID 67467406, compound

HRID 42450Notes

Reaction equation

HRID 42450 reaction equation
Br[C:2]1[N:3]([CH:17]([CH3:19])[CH3:18])[C:4]2[CH:5]=[C:6]([Cl:16])[CH:7]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[C:9]=2[C:10]=1[CH3:11].[CH3:20]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>O1CCOCC1.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>[Cl:16][C:6]1[CH:7]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[C:9]2[C:10]([CH3:11])=[C:2]([CH3:20])[N:3]([CH:17]([CH3:19])[CH3:18])[C:4]=2[CH:5]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 574072Trimethylboroxine2×HCID 67465593methyl 2-bromo-6-chloro-1-isopropyl-3-methyl-1H-indole-4-carboxylate

Product 1

HCID 67467406HCID 67467406, compoundYield 81.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of methyl 2-bromo-6-chloro-1-isopropyl-3-methyl-1H-indole-4-carboxylate (0.50 g, 1.451 mmol), Trimethylboroxine (0.30 mL, 2.146 mmol) and potassium carbonate (0.31 g, 2.243 mmol) in 1,4-Dioxane (20 mL) under N2 was added palladium tetrakis (0.18 g, 0.156 mmol). The reaction was heated to 110° C. and stirred for 18 hr. After 3 hr an additional 100 uL Trimethylboroxine was added. The reaction was concentrated under vacuum, taken up in EtOAc, washed with water, dried (MgSO4), filtered and concentrated under vacuum. Purification by silica gel chromatography (Analogix, SF25-60 g, 0 to 10% EtOAc in hexanes) gave the product methyl 6-chloro-1-isopropyl-2,3-dimethyl-1H-indole-4-carboxylate (0.33 g, 1.180 mmol, 81% yield) as a clear thick oil. 1H NMR (400 MHz, DMSO-d6) δ=7.80 (d, J=2.0 Hz, 1H), 7.28 (d, J=1.8 Hz, 1H), 4.81 (dt, J=6.9, 13.9 Hz, 1H), 3.87 (s, 3H), 2.39 (s, 3H), 2.13 (s, 3H), 1.51 (d, J=7.1 Hz, 6H) MS (ES)+m/e 280.1 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated under vacuum
  2. washwashed with water
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customPurification by silica gel chromatography (Analogix

Sources & evidence

ORD record
ord-78eecfbecc5f42d89274db6f4eee675c
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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