Triethylamine → 2-{[2-(hex-1-yn-1-yl)-1,3-thiazol-4-yl]methoxy}-1H-isoindole-1,3(2H)-dione

HRID 2039682

Reaction equation

HRID 2039682 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([CH2:7][O:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[N:6]=1.[CH:20]#[C:21][CH2:22][CH2:23][CH2:24][CH3:25].C(N(CC)CC)C>O1CCCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].[Cu](I)I>[C:20]([C:2]1[S:3][CH:4]=[C:5]([CH2:7][O:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[N:6]=1)#[C:21][CH2:22][CH2:23][CH2:24][CH3:25]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 127321-HexyneHCID 674242932-[(2-bromo-1,3-thiazol-4-yl)methoxy]-1H-isoindole-1,3(2H)-dione

Product 1

HCID 674260462-{[2-(hex-1-yn-1-yl)-1,3-thiazol-4-yl]methoxy}-1H-isoindole-1,3(2H)-dioneYield 59%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[(2-bromo-1,3-thiazol-4-yl)methoxy]-1H-isoindole-1,3(2H)-dione (23.1 g, 68.1 mmol) in dry tetrahydrofuran (300 mL) were added 1-hexyne (11.2 g, 136 mmol), triethylamine (13.8 g, 136 mmol). The reaction mixture was degassed by blowing a flow of Argon through it, then palladium tetrakis(triphenylphosphine) (3.94 g, 3.41 mmol) and copper iodide (1.30 g, 6.81 mmol) were added. After stirring at room temperature for 21 h under argon, the mixture was concentrated in vacuo, diluted with water (800 mL) and ethyl acetate (900 mL), the organic layer was washed with water, dried (MgSO4) and concentrated in vacuo. Purification on silica gel afforded 2-{[2-(hex-1-yn-1-yl)-1,3-thiazol-4-yl]methoxy}-1H-isoindole-1,3(2H)-dione [13.6 g, yield 59%; HPLC/MS: m/z=341 (M+H); log P(HCOOH)=3.78].

Workup

  1. customThe reaction mixture was degassed
  2. concentrationthe mixture was concentrated in vacuo
  3. additiondiluted with water (800 mL) and ethyl acetate (900 mL)
  4. washthe organic layer was washed with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification on silica gel

Sources & evidence

ORD record
ord-a5fec88c4a134e67ba5d586535e0548f
Source dataset
uspto-grants-2013_11
Patent number
US08580799B2

Linked notes

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