Triethylamine → HCID 58114127, compound

HRID 1046450Notes

Reaction equation

HRID 1046450 reaction equation
[CH3:1][C:2]([CH3:8])([C:6]#[CH:7])[CH2:3][CH2:4][OH:5].[CH3:9][O:10][C:11]([C:13]1[S:14][C:15](I)=[CH:16][C:17]=1[N:18]([CH:28]1[CH2:33][CH2:32][CH:31]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH2:30][CH2:29]1)[C:19]([CH:21]1[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])=[O:12].C(N(CC)CC)C>CN(C=O)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>[CH3:9][O:10][C:11]([C:13]1[S:14][C:15]([C:7]#[C:6][C:2]([CH3:8])([CH3:1])[CH2:3][CH2:4][OH:5])=[CH:16][C:17]=1[N:18]([CH:28]1[CH2:29][CH2:30][CH:31]([O:34][Si:35]([C:38]([CH3:39])([CH3:41])[CH3:40])([CH3:36])[CH3:37])[CH2:32][CH2:33]1)[C:19]([CH:21]1[CH2:22][CH2:23][CH:24]([CH3:27])[CH2:25][CH2:26]1)=[O:20])=[O:12]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 102407894-Pentyn-1-ol, 3,3-dimethyl-HCID 58113953HCID 58113953, compound

Product 1

HCID 58114127HCID 58114127, compoundYield 90.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of the 3,3-dimethyl-pent-4-yn-1-ol (600 mg, 5.36 mmol), 3-[[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (2767 mg, 4.46 mmol) and triethylamine (10.8 mL, 77.48 mmol) in DMF (25 mL) was degassed for 10 minutes with nitrogen. PdCl2(PPh3)2 (314 mg, 0.45 mmol) and CuI (170 mg, 0.90 mmol) was added and the resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction was placed in a 80° C. oil bath and heated for 3.5 h. The reaction was cooled and partitioned between ethyl acetate and sat. NaHCO3. The organic layer was separated, washed with 5% LiCl, brine, dried over Na2SO4 and concentrated to give a dark brown foam. Purification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes then 5% methanol in ethyl acetate provided 3-[[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-(5-hydroxy-3,3-dimethyl-pent-1-ynyl)-thiophene-2-carboxylic acid methyl ester (2.43 g, 90%) as a pale yellow foam.

Workup

  1. customthe resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
  2. customwas placed in a 80° C.
  3. temperatureheated for 3.5 h
  4. temperatureThe reaction was cooled
  5. custompartitioned between ethyl acetate and sat. NaHCO3
  6. customThe organic layer was separated
  7. washwashed with 5% LiCl, brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customto give a dark brown foam
  11. customPurification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-799a212e550749f296659c109deed61d
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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