Potassium Fluoride → Methyl 6-cyclohexyl-5-(3-formyl-2-thienyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 1008979Notes

Reaction equation

HRID 1008979 reaction equation
Br[C:2]1[N:6]([CH2:7][C:8]([O:10][C:11](C)(C)C)=[O:9])[C:5]2[CH:15]=[C:16]([C:18]([O:20][CH3:21])=[O:19])[S:17][C:4]=2[C:3]=1[CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.[CH:28]([C:30]1[CH:34]=[CH:33][S:32][C:31]=1B(O)O)=[O:29].[F-].[K+]>O1CCOCC1.CC(P(C(C)(C)C)C(C)(C)C)(C)C.CC(P(C(C)(C)C)C(C)(C)C)(C)C.[Pd]>[CH:22]1([C:3]2[C:4]3[S:17][C:16]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][C:5]=3[N:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])[C:2]=2[C:31]2[S:32][CH:33]=[CH:34][C:30]=2[CH:28]=[O:29])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 27734293-Formyl-2-thiopheneboronic Acid (contains varying amounts of Anhydride)HCID 67298685methyl 5-bromo-4-(2-tert-butoxy-2-oxoethyl)-6-cyclohexyl-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 86629782Methyl 6-cyclohexyl-5-(3-formyl-2-thienyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 65%

Reagents, catalysts & solvents 2

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Methyl 5-bromo-6-cyclohexyl-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate (prepared in analogy to Example 7, Step 2, substituting tert-butyl bromoacetate with methyl bromo acetate) and (3-formyl-2-thienyl)boronic acid (1.2 eq.) were dissolved in dioxane (0.1 M) and treated with spray-dried KF (3.3 eq.). The solution was degassed by bubbling argon and Pd(t-Bu3P)2 (0.24 eq.) was added, and the reaction mixture was left stirring overnight; the mixture was then absorbed on silica gel and the title compound isolated by chromatography (PE/EtOAc 9:1). Yield: 65%. 1H-NMR (400 MHz, CDCl3, 300 K, δ) 9.62 (s, 1H), 7.63 (s, 1H), 7.61 (d, 1H, J 5.5), 7.50 (d, 1H, J 5.5), 4.62 (s, 2H), 3.91 (s, 3H), 3.67 (s, 3H), 2.46-2.37 (m, 1H), 1.80-0.80 (m, 10H); MS (ES+) m/z 446 (M+H)+.

Workup

  1. customThe solution was degassed
  2. additionwas added
  3. waitthe reaction mixture was left
  4. customthe mixture was then absorbed on silica gel

Sources & evidence

ORD record
ord-e3e2a58794584d79a2b579523a7e76b5
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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