Triethylsilane → 3-[(4-Hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carbox

HRID 1046447Notes

Reaction equation

HRID 1046447 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([I:27])=[CH:8][C:9]=1[N:10]([C:18]([CH:20]1[CH2:25][CH2:24][CH:23]([CH3:26])[CH2:22][CH2:21]1)=[O:19])[CH:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1)=[O:4].C[Si](C)(C)OC1CCOC1.C([SiH](CC)CC)C.C([O-])(O)=O.[Na+]>[N+](C)([O-])=O.CO>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([I:27])=[CH:8][C:9]=1[N:10]([CH:11]1[CH2:12][CH2:13][CH:14]([OH:17])[CH2:15][CH2:16]1)[C:18]([CH:20]1[CH2:21][CH2:22][CH:23]([CH3:26])[CH2:24][CH2:25]1)=[O:19])=[O:4]

Participants

7

Reactant 4

HCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 581141515-Iodo-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl esterHCID 66849751Trimethyl-(tetrahydro-furan-3-yloxy)-silane

Product 1

HCID 249893473-[(4-Hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxYield 50.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6375NitromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 5-iodo-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester (2.5 g, 4.96 mmol) and FeCl3 (41 mg, 0.252 mmol) in nitromethane (15.0 mL) cooled to 0° C. was added neat trimethyl-(tetrahydro-furan-3-yloxy)-silane (955 mg, 5.95 mmol) followed by the dropwise addition of triethylsilane (0.947 mL, 5.92 mmol). The reaction was allowed to slowly warm to room temperature and stirred overnight. Sat. NaHCO3 was added and the reaction mixture was extracted with dichloromethane. The organic layer was washed with brine, dried over Na2SO4 and concentrated to give a solid. The crude solid was heated in methanol, cooled and collected by filtration to provide 3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (1.27 g, 44%) as a colorless solid.

Workup

  1. temperatureto slowly warm to room temperature
  2. extractionthe reaction mixture was extracted with dichloromethane
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give a solid
  7. temperaturecooled
  8. filtrationcollected by filtration

Sources & evidence

ORD record
ord-272856e64a3b4111a1792c77d4fe2078
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

Loading…