2-Methyl-3-butyn-2-ol → HCID 66883551, compound

HRID 915370Notes

Reaction equation

HRID 915370 reaction equation
[CH3:1][C:2]1[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:14](OS(C(F)(F)F)(=O)=O)=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:23].CCN(CC)CC.[CH3:36][C:37]([OH:41])([C:39]#[CH:40])[CH3:38]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]1[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:14]([C:40]#[C:39][C:37]([OH:41])([CH3:38])[CH3:36])=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:23]

Participants

6

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 86594619HCID 86594619, compound

Product 1

HCID 66883551HCID 66883551, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of trifluoromethanesulfonic acid 2-(2,4-dimethylbenzyl)-1-oxo-1,2-dihydro-isoquinolin-3-yl ester (50 mg, 0.12 mmol) in THF (1.5 mL) was added Et3N (83 μL, 0.59 mmol). The resulting mixture was then degassed by bubbling argon through the solution for twenty minutes. The degassed solution was then treated with 2-methyl-but-3-yn-2-ol (23 μL, 0.24 mmol) followed by tetrakistriphenylphosphine Pd(0) (13 mg, 12 μmol) and Cul (˜2 mg, ˜12 μmol). The resulting suspension was stirred at ambient temperature for 16 hours, then filtered through a short plug of silica gel eluting with ethyl acetate. The filtrate was concentrated under reduced pressure to afford the crude product. The crude product was purified by silica gel column chromatography eluting with a gradient from 0% to 50% ethyl acetate/hexane on a silica column. The product peak was collected to afford 2-(2,4-dimethylbenzyl)-3-(3-hydroxy-3-methylbut-1-ynyl)-2H-isoquinolin-1-one (27 mg, 65% yield) as a white solid. 1H-NMR (400 MHz, CDCl3): δ 8.43 (1H, d, J=8.1 Hz), 7.70-7.64 (1H, m), 7.75-7.49 (2H, m), 7.0 (1H, s), 6.89-6.85 (2H, m), 6.65-6.61 (1H, m), 5.42 (2H, s), 2.40 (3H, s), 2.26 (3H, s), 1.40 (6H, s). ppm.

Workup

  1. customThe resulting mixture was then degassed
  2. customby bubbling argon through the solution for twenty minutes
  3. filtrationfiltered through a short plug of silica gel eluting with ethyl acetate
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customto afford the crude product
  6. customThe crude product was purified by silica gel column chromatography
  7. washeluting with a gradient from 0% to 50% ethyl acetate/hexane on a silica column
  8. customThe product peak was collected

Sources & evidence

ORD record
ord-4c9317f39a054332a7bd8c28adb52919
Source dataset
uspto-grants-2007_09
Patent number
US07265131B2

Reaction notes

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