3,3-Dimethyl-1-butyne → HCID 178499344, compound

HRID 1675535Notes

Reaction equation

HRID 1675535 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](Br)=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].[CH3:28][C:29]([CH3:33])([CH3:32])[C:30]#[CH:31]>CN(C=O)C.C(N(CC)CC)C.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:31]#[C:30][C:29]([CH3:33])([CH3:32])[CH3:28])=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4]

Participants

6

Reactant 2

HCID 135123,3-Dimethyl-1-butyneHCID 178499257HCID 178499257, compound

Product 1

HCID 178499344HCID 178499344, compound

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of compounds 5-bromo-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (500 mg, 1.09 mmol) and 3,3-Dimethyl-but-1-yne (385 mg, 4.69 mmol) in DMF (0.5 mL), triethylamine (1.06 mL) and tris(dibenzylideneacetone) dipalladium (0) (70 mg, 0.08 mmol) are added and the reaction mixture is stirred under reflux conditions for 16 h under a N2 atmosphere. DMF and triethylamine are removed under reduced pressure and the residue is partitioned between water and ethyl acetate. The organic layer is separated, dried (Na2SO4), concentrated and the residue is purified by column chromatography using ethyl acetate and hexane (1:2) as eluent to obtain 5-(3,3-dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester as a solid, 330 mg (66%).

Workup

  1. customDMF and triethylamine are removed under reduced pressure
  2. customthe residue is partitioned between water and ethyl acetate
  3. customThe organic layer is separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customthe residue is purified by column chromatography

Sources & evidence

ORD record
ord-590b61501b6a43de8825054121f7dc3c
Source dataset
uspto-grants-2011_08
Patent number
US08003685B2

Reaction notes

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