Toluene → HCID 86698714, compound

HRID 338371Notes

Reaction equation

HRID 338371 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.Cl.Br[C:25]1[CH:30]=[CH:29][C:28]([CH:31]2[CH2:34][CH2:33][NH:32]2)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.C(O)C>[NH:32]1[CH2:33][CH2:34][CH:31]1[C:28]1[CH:29]=[CH:30][C:25]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[Cl:1])[NH:8][CH:7]=[C:6]3[C:11]([O:13][CH3:14])=[O:12])=[CH:26][CH:27]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylateHCID 866987151467062-15-2

Product 1

HCID 86698714HCID 86698714, compoundYield 379.6%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 6-Chloro-5-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-1H-indole-3-carboxylate (50 mg, 0.16 mmol), 2-(4-bromophenyl)azetidine hydrochloride (400 mg, 1.24 mmol), 2M aqueous potassium carbonate (3.11 mL, 6.22 mmol), toluene (9 mL), and ethanol (3 mL) was sparged with nitrogen for 10 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (46 mg, 0.056 mmol). The reaction mixture was heated to 100° C. and stirred. After 2 hours the reaction was cooled to room temperature, diluted with ethyl acetate, washed with water and saturated brine, dried over magnesium sulfate, filtered and concentrated in vacuo to afford a yellow oil, which was purified by flash chromatography (40 g silica, 0-40% methanol/ethyl acetate (1% TEA modifier), 24 column volumes). Product fractions were combined and concentrated in vacuo to afford the title compound as a yellow solid (207 mg, 49% yield). MS (ES+) 341.2 (M+H)+; 1H NMR (500 MHz, CD3OD) δ 7.98 (d, J=3.90 Hz, 2H), 7.56 (s, 1H), 7.41 (s, 4H), 5.02 (t, J=8.17 Hz, 1H), 3.84 (s, 3H), 3.68-3.79 (m, 1H), 3.34-3.45 (m, 1H), 2.47-2.66 (m, 2H).

Workup

  1. customwas sparged with nitrogen for 10 minutes
  2. temperatureAfter 2 hours the reaction was cooled to room temperature
  3. washwashed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow oil, which
  8. customwas purified by flash chromatography (40 g silica, 0-40% methanol/ethyl acetate (1% TEA modifier), 24 column volumes)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-44659f953fa342f1a5b8847e7e59f272
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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