Trimethylsilylacetylene → 2-Ethynyl-7-hydroxy-6-methoxy-3-(3,4,5-trimethoxybenzoyl)-benzofuran

HRID 529241Notes

Reaction equation

HRID 529241 reaction equation
Br[C:2]1[O:3][C:4]2[C:24]([O:25]C(=O)C)=[C:23]([O:29][CH3:30])[CH:22]=[CH:21][C:5]=2[C:6]=1[C:7](=[O:20])[C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([O:16][CH3:17])=[C:10]([O:18][CH3:19])[CH:9]=1.C[Si]([C:35]#[CH:36])(C)C>ClCCl.C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:35]([C:2]1[O:3][C:4]2[C:24]([OH:25])=[C:23]([O:29][CH3:30])[CH:22]=[CH:21][C:5]=2[C:6]=1[C:7](=[O:20])[C:8]1[CH:9]=[C:10]([O:18][CH3:19])[C:11]([O:16][CH3:17])=[C:12]([O:14][CH3:15])[CH:13]=1)#[CH:36]

Participants

7

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 247865602-Bromo-7-acetoxy-3-(3,4,5-trimethoxybenzoyl)-6-methoxybenzofuran

Product 1

HCID 248800482-Ethynyl-7-hydroxy-6-methoxy-3-(3,4,5-trimethoxybenzoyl)-benzofuranYield 26.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 2-Bromo-7-acetoxy-3-(3,4,5-trimethoxybenzoyl)-6-methoxybenzofuran (50 mg, 0.10 mmol) in dichloromethane (1 ml) and triethylamine (0.5 ml) was added Pd(Ph3P)2Cl2 (3.5 mg, 5 mol %) and the reaction vessel was evacuated and backfilled with nitrogen three times. Trimethylsilylacetylene (30 mg, 0.30 mmol) and copper (I) iodide (3 mg, 15 mol %) were added sequentially and the resulting dark mixture was stirred for two hours at room temperature. After this time the reaction was concentrated under vacuum and treated with methanol (1 ml) and potassium hydroxide (30 mg, excess). Stirring was continued for 0.5 hours then the crude mixture was concentrated onto silica and chromatographed (silica gel, gradient elution—2:1 hexanes:ethyl acetate, 1:1 hexanes:ethyl acetate) to afford the product as a tan solid (10 mg, 26%); 1H NMR (CDCl3) δ 7.26 (d, J=8.6 Hz, 1H), 7.20 (s, 2H), 6.98 (d, J=8.6 Hz, 1H), 3.96 (s, 3H), 3.93 (s, 3H), 3.87 (s, 6H), 3.51 (s, 1H); LRMS (ESI) m/z=383 (M+H+).

Workup

  1. customthe reaction vessel was evacuated
  2. concentrationAfter this time the reaction was concentrated under vacuum
  3. additiontreated with methanol (1 ml) and potassium hydroxide (30 mg, excess)
  4. stirringStirring
  5. waitwas continued for 0.5 hours
  6. concentrationthe crude mixture was concentrated onto silica
  7. customchromatographed (silica gel, gradient elution—2:1 hexanes:ethyl acetate, 1:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-1a1beb9404f441929f332ebf2e6e96a2
Source dataset
uspto-grants-2016_05
Patent number
US09346842B2

Reaction notes

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