Hydrochloric Acid → Tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acid

HRID 2406387Notes

Reaction equation

HRID 2406387 reaction equation
S1C2C=CC(B(O)O)=CC=2N=C1.C([O:15][C:16](=[O:38])[CH:17]([C:23]1[C:24]([I:37])=[C:25]2[C:32]3[CH2:33][CH2:34][CH2:35][CH2:36][C:31]=3[S:30][C:26]2=[N:27][C:28]=1[CH3:29])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])C.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Li+].Cl>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1>[C:19]([O:18][CH:17]([C:23]1[C:24]([I:37])=[C:25]2[C:32]3[CH2:33][CH2:34][CH2:35][CH2:36][C:31]=3[S:30][C:26]2=[N:27][C:28]=1[CH3:29])[C:16]([OH:38])=[O:15])([CH3:22])([CH3:20])[CH3:21]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 10796Cesium carbonate2×HCID 18452959HCID 18452959, compoundHCID 69672858HCID 69672858, compound

Product 1

HCID 67606758Tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acidYield 23%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-Benzothiazole-boronic acid (150 μmol) and ethyl-2-tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetate (Preparation 11, 1 mL of a 0.1M solution in dioxane, 100 μmol) were added to a reaction vial. A 1M solution of caesium carbonate (2004, 200 μmol) in water was then added, followed by 5 μmol of Pd(dppf)Cl2 and the whole stirred at 100° C. for 16 h before cooling to room temperature and evaporation of the solution under reduced pressure to give a yellow residue. A 2M solution of lithium hydroxide in water (2004, 400 μmol) was added to each vial, followed by 1 mL of THF, and the mixture was shaken at room temperature for 16 h. The pH of the solution was adjusted to neutral using a 1M aqueous solution of hydrochloric acid, before the mixture was evaporated to dryness under reduced pressure and the residue then purified by preparative HPLC on a C18 column, using a mixture of acetonitrile and water as the mobile phase. Evaporation of the appropriate fractions under reduced pressure provided the title compound (11 mg, 23%) as a white solid. ESI/APC(+): 467 (M+H).

Workup

  1. additionwere added to a reaction vial
  2. temperaturebefore cooling to room temperature
  3. customevaporation of the solution under reduced pressure
  4. customto give a yellow residue
  5. stirringthe mixture was shaken at room temperature for 16 h
  6. custombefore the mixture was evaporated to dryness under reduced pressure
  7. customthe residue then purified by preparative HPLC on a C18 column
  8. additiona mixture of acetonitrile and water as the mobile phase
  9. customEvaporation of the appropriate fractions under reduced pressure

Sources & evidence

ORD record
ord-c74b84a9544a4883b76c1d09de86f902
Source dataset
uspto-grants-2014_08
Patent number
US08809363B2

Reaction notes

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