Tetrahydrofuran → HCID 86698838, compound

HRID 338502Notes

Reaction equation

HRID 338502 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.Br[C:24]1[CH:29]=[CH:28][C:27]([CH:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[CH:26][CH:25]=1.O1CCCC1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C>[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]=1[C:24]1[CH:25]=[CH:26][C:27]([CH:30]2[CH2:31][CH2:32][O:33][CH2:34][CH2:35]2)=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 198177774-(4-Bromophenyl)oxaneHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate

Product 1

HCID 86698838HCID 86698838, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (440 mg, 1.37 mmol) and 4-(4-bromophenyl)tetrahydro-2H-pyran (300 mg, 1.24 mmol) in toluene (6 mL), ethanol (3 mL), and tetrahydrofuran (3 mL) followed by the addition of 2M potassium carbonate aqueous (3 mL, 6 mmol). Nitrogen was bubbled through the reaction for 5 minutes then [1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium-dichloromethane complex (120 mg, 0.143 mmol) was added and the reaction heated to 115° C. for 16 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure. The crude product was purified using the Biotage Isolera One (SNAP 50 g silica gel column) and eluting with a gradient of 0-100% ethyl acetate/heptane yielding 360 mg of the title compound as a solid.

Workup

  1. customNitrogen was bubbled through the reaction for 5 minutes
  2. addition[1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium-dichloromethane complex (120 mg, 0.143 mmol) was added
  3. temperatureThe reaction was then cooled to room temperature
  4. filtrationfiltered through a pad of celite
  5. washwashing with ethyl acetate
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe crude product was purified
  8. washeluting with a gradient of 0-100% ethyl acetate/heptane yielding 360 mg of the title compound as a solid

Sources & evidence

ORD record
ord-a8346fcc736549098fa94f1b0095ba96
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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