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

HRID 1008992Notes

Reaction equation

HRID 1008992 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][CH3:18])=[O:16])[S:14][C:4]=2[C:3]=1[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[F:25].[CH:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O)=[O:27].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH:19]1[C:3]1[C:4]2[S:14][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:12][C:5]=2[N:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])[C:2]=1[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[CH:26]=[O:27]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2921892-Formylphenylboronic acidHCID 67298644HCID 67298644, compound

Product 1

HCID 86629784methyl 6-(2-fluorocyclohexyl)-5-(2-formylphenyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 56%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution (0.1 M) of methyl 5-bromo-6-(2-fluorocyclohexyl)-4-(2-methoxy-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate in dioxane was treated with (2-formylphenyl)boronic acid (1.5 eq.); aq. Na2CO3-solution (2 N, 8.5 eq.) was added and the solution was degassed, and then treated with Pd(PPh3)4 (0.1 eq.). A balloon with argon was installed, the mixture was placed in an oil bath preheated at 115° C. and stirred for 30 min, then cooled and diluted with EtOAc and brine. The organic phase was separated, washed with 1N HCl and brine, dried and concentrated. The residue was purified by chromatography (PE/EtOAc) to give the title compound (56%); some starting material (21%) was recovered. 1H-NMR (400 MHz, CDCl3, 300K, δ) 9.78&9.85* (bs, 1H.), 8.06 (dd, 1H, J 7.7, 1.3), 7.67 (s, 1H), 7.73-7.60 (m, 2H), 7.44 (bd, 1H, J 7.5), 4.50&4.55* (d, 1H, J 17.8&17.6), 4.44&4.48* (d, 1H, J 17.8&17.6), 4.73-4.49 (m, 1H), 3.91 (s, 3H), 3.62&3.63* (s, 3H), 2.42-2.34 (m, 1H), 2.18-2.12 (m, 1H), 1.83-1.07 (m, 7H); MS (ES+) m/z 458 (M+H)+. * Refers to two different conformers.

Workup

  1. customthe solution was degassed
  2. customthe mixture was placed in an oil bath
  3. custompreheated at 115° C.
  4. temperaturecooled
  5. customThe organic phase was separated
  6. washwashed with 1N HCl and brine
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (PE/EtOAc)

Sources & evidence

ORD record
ord-6c3efd7dd30e40d39e6807c564465ed7
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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