Triethylamine → HCID 178499327, compound

HRID 1675540Notes

Reaction equation

HRID 1675540 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](I)=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:29][CH2:28][C:23]2([O:27][CH2:26][CH2:25][O:24]2)[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].C(N(CC)CC)C.[CH3:38][C:39]([CH3:43])([CH3:42])[C:40]#[CH:41]>[Cu](I)I.[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.CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:41]#[C:40][C:39]([CH3:43])([CH3:42])[CH3:38])=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:29][CH2:28][C:23]2([O:27][CH2:26][CH2:25][O:24]2)[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

7

Reactant 3

HCID 8471TriethylamineHCID 135123,3-Dimethyl-1-butyneHCID 178499356HCID 178499356, compound

Product 1

HCID 178499327HCID 178499327, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a 25 mL RBF under nitrogen, 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (1 eq.), copper iodide (0.025 eq.) and tris(dibenzylideneacetone) dipalladium (0) (0.01 eq.) are taken. DMF, triethylamine (2.5 eq.) and 3,3-dimethyl-but-1-yne (2 eq.) are added and the reaction mixture is stirred at 40° C. for 2 h under a N2 atmosphere. The reaction mixture is filtered on celite and washed with ethyl acetate. The solution is diluted with water and extracted 2 times with ethyl acetate. The organic phases are combined and washed 3 times with water. The organic layer is separated, dried (Na2SO4), evaporated to about 2 mL and then 8 mL of heptane is added. It is evaporated to 2-4 mL and cooled in an ice bath. The formed white solid is filtered, washed with heptane and dried in oven to obtain 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester.

Workup

  1. filtrationThe reaction mixture is filtered on celite
  2. washwashed with ethyl acetate
  3. additionThe solution is diluted with water
  4. extractionextracted 2 times with ethyl acetate
  5. washwashed 3 times with water
  6. customThe organic layer is separated
  7. dry with materialdried (Na2SO4)
  8. customevaporated to about 2 mL
  9. addition8 mL of heptane is added
  10. customIt is evaporated to 2-4 mL
  11. temperaturecooled in an ice bath
  12. filtrationThe formed white solid is filtered
  13. washwashed with heptane
  14. customdried in oven

Sources & evidence

ORD record
ord-c6d9aaa10ef445edb4dc92743ed645ba
Source dataset
uspto-grants-2011_08
Patent number
US08003685B2

Reaction notes

Loading…