Sodium Carbonate → tert-butyl 6-cyclohexyl-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 1008964Notes

Reaction equation

HRID 1008964 reaction equation
Br[C:2]1[N:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])[C:5]2[CH:12]=[C:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[S:14][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:35]=[CH:34][CH:33]=[CH:32][C:31]=1B(O)O)=[O:29].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.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>[CH:22]1([C:3]2[C:4]3[S:14][C:13]([C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])=[CH:12][C:5]=3[N:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])[C:2]=2[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[CH:28]=[O:29])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2921892-Formylphenylboronic acidHCID 67298890tert-butyl 5-bromo-6-cyclohexyl-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 86629778tert-butyl 6-cyclohexyl-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 68%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 5-bromo-6-cyclohexyl-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate (1 eq., from Step 3) and 2-formyl-phenylboronic acid (1.5 eq.) were dissolved in dioxane (0.1 M) and treated with 2 M Na2CO3 solution (2 eq.). The solution was degassed by bubbling argon through it and Pd(PPh3)2Cl2 (0.1 eq.) was added. The reaction mixture was heated to reflux for 20 min then allowed to cool down to RT, diluted with EtOAc and washed with 1 N hydrochloric acid and with brine. The organic layer was dried over sodium sulfate, evaporated in vacuo and the residue purified by chromatography (PE:EtOAc, 9:1) to afford the pure title compound (68%) as a solid. 1H-NMR (400 MHz, DMSO-d6, 300 K, δ) 9.70 (s, 1H), 7.96 (dd, J 7.7, 1.3, 1H), 7.91 (s, 1H), 7.84 (dt, J 7.6, 1.5, 1H), 7.80 (t, J 7.7, 1H), 7.47 (d, J 7.6, 1H), 4.93 (d, J 18.2, 1H), 4.76 (d, J 18.2, 1H), 3.48 (s, 3H), 2.15-2.08 (m, 1H), 1.73-1.02 (m, 10H), 1.52 (s, 9H). MS (ES+) m/z: 482 [M+H]+.

Workup

  1. customThe solution was degassed
  2. additionwas added
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 20 min
  5. washwashed with 1 N hydrochloric acid and with brine
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customevaporated in vacuo
  8. customthe residue purified by chromatography (PE:EtOAc, 9:1)

Sources & evidence

ORD record
ord-23cf8d928904492ea45b7188f53716a7
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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