2-Methyl-3-butyn-2-ol → HCID 11163443, compound

HRID 1042568Notes

Reaction equation

HRID 1042568 reaction equation
I[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.[CH3:26][C:27](O)(C#C)C.[OH-].[K+]>C1COCC1.C(N(CC)CC)C.C(O)(C)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>[C:26]([C:2]1[N:3]=[CH:4][N:5]([C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1)#[CH:27]

Participants

8

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 14797Potassium HydroxideHCID 6182524-Iodo-1-tritylimidazole

Product 1

HCID 11163443HCID 11163443, compoundYield 41%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 4-iodo-1-trityl-1H-imidazole (830 mg, 1.96 mmol) and Pd(Ph3P)2Cl2 (40 mg, 3 mol %) in THF (8 mL) and triethylamine (2 mL) was added 2-methyl-but-3-yn-2-ol (0.30 mL, 3.10 mmol) and the reaction vessel was evacuated and backfilled with nitrogen three times to remove atmospheric oxygen. Copper (I) iodide (40 mg, 10 mol %) was added and the reaction was stirred at room temperature for 5 h. After this time the solvent was removed under vacuum and the residue was filtered through a plug of silica gel (eluent=2:1 hexane:ethyl acetate) to give the crude alkynol product. This material was dissolved in isopropanol (10 mL) and treated with potassium hydroxide (150 mg, 2.67 mmol). The reaction mixture was heated to 70° C. for 4 h and then concentrated under vacuum and purified by silica-gel chromatography (eluent=4:1 hexane:ethyl acetate) to afford the product as a white solid (258 mg, 41% yield over two steps). 1H-NMR (CDCl3) δ 7.41 (s, 1H), 7.38-7.31 (m, 9H), 7.13-7.07 (m, 6H), 7.05 (d, J=1 Hz), 3.05 (s, 1H).

Workup

  1. customthe reaction vessel was evacuated
  2. customto remove atmospheric oxygen
  3. additionCopper (I) iodide (40 mg, 10 mol %) was added
  4. customAfter this time the solvent was removed under vacuum
  5. filtrationthe residue was filtered through a plug of silica gel (eluent=2:1 hexane:ethyl acetate)
  6. customto give the crude alkynol product
  7. temperatureThe reaction mixture was heated to 70° C. for 4 h
  8. concentrationconcentrated under vacuum
  9. custompurified by silica-gel chromatography (eluent=4:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-1a40578a47f74dd39d41e173c694b219
Source dataset
uspto-grants-2013_10
Patent number
US08557982B2

Reaction notes

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