Toluene → HCID 86698788, compound

HRID 338454Notes

Reaction equation

HRID 338454 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.[CH2:23]([O:30][CH2:31][C:32]1([C:36]2[CH:41]=[CH:40][C:39](Br)=[CH:38][CH:37]=2)[CH2:35][O:34][CH2:33]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C(O)C>[CH2:23]([O:30][CH2:31][C:32]1([C:36]2[CH:41]=[CH:40][C:39]([C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][C:2]=3[Cl:1])[NH:8][CH:7]=[C:6]4[C:11]([O:13][CH3:14])=[O:12])=[CH:38][CH:37]=2)[CH2:33][O:34][CH2:35]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylateHCID 86698787HCID 86698787, compound

Product 1

HCID 86698788HCID 86698788, compoundYield 62.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of methyl 6-Chloro-5-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-1H-indole-3-carboxylate (241 mg, 0.75 mmol), 3-Benzyloxymethyl-3-(4-bromo-phenyl)-oxetane (250 mg, 0.75 mmol), 2M aqueous potassium carbonate (1.51 mL, 3 mmol), toluene (9 mL), and ethanol (3 mL) was sparged with N2 for 10 minutes, then treated with [1,1′bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (29 mg, 0.035 mmol). The reaction mixture was heated to 100 degrees 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 brown oil, which was purified by flash chromatography (40 g silica, 10-60% ethyl acetate/heptane, 17 column volumes). Product fractions were combined and concentrated in vacuo to afford the title compound as a colorless solid (215 mg, 62% yield). MS (ES+) 462 (M+H)+; 1H NMR (500 MHz, CD3OD) δ ppm 8.04 (s, 1H), 8.02 (s, 1H), 7.99 (s, 1H), 7.43-7.57 (m, 4H), 7.23-7.34 (m, 5H), 4.90-5.01 (m, 4H), 4.58 (s, 2H), 3.90 (s, 3H), 3.88 (s, 2H).

Workup

  1. customwas sparged with N2 for 10 minutes
  2. temperatureThe reaction mixture was heated to 100 degrees
  3. washwashed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a brown oil, which
  8. customwas purified by flash chromatography (40 g silica, 10-60% ethyl acetate/heptane, 17 column volumes)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c2d0fc008661428093f94c469f989a3a
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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