Hydrochloric Acid → HCID 86760257, compound

HRID 2215749Notes

Reaction equation

HRID 2215749 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]#[N:14])=[CH:4]1.Br[CH2:16][CH2:17][CH2:18][O:19]C(=O)C.[OH-:23].[K+].Cl>CN(C=O)C.CCOC(C)=O.C(O)(C)(C)C>[OH:19][CH2:18][CH2:17][CH2:16][C:4]1[NH:3][C:11]2[C:6]([C:5]=1[CH2:12][C:13]([NH2:14])=[O:23])=[CH:7][CH:8]=[CH:9][CH:10]=2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 351795Indole-3-acetonitrileHCID 122357751-Propanol, 3-bromo-, 1-acetate

Product 1

HCID 86760257HCID 86760257, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of NaH (3.59 g, 89.6 mmol) in DMF (20 mL) cooled to 0° C. was added a solution of indole-3-acetonitrile (10.0 g, 64.0 mmol) in DMF (80 mL) and the mixture was allowed to come to rt and stir for 30 min, becoming dark brown. It was cooled back to 0° C. and 3-bromopropylacetate (89.6 mmol) was added by syringe, slowly to control foaming. The reaction was stirred vigorously at rt for 4 h and then diluted with EtOAc and quenched with a 0.5 M solution of HCl. The organic layer was washed with a saturated aqueous solution of NaCl, dried (MgSO4) and the solvent removed in vacuo to give a brown oil. This was dissolved in t- butanol (175 mL) and freshly ground KOH (42.2 g, 640 mmol) was added with vigourous stirring. The reaction was heated to reflux for 1.5 h. It was then cooled to 30° C. and poured onto ice (500 mL). 6N HCl was added until the pH of the mixture was 1.0. The reaction was diluted with EtOAc the layers separated. The organic layer was washed with a saturated aqueous solution of NaCl, dried (MgSO4) and the solvent removed in vacuo to give a brown oil which was purified by column chromatography (Start 1:1 hexanes:acetone until product begins eluting, wash off with 95:5 acetone:MeOH) to afford 374076 the title compound (60%) as a creme colored solid.

Workup

  1. customto come to rt
  2. stirringThe reaction was stirred vigorously at rt for 4 h
  3. customquenched with a 0.5 M solution of HCl
  4. washThe organic layer was washed with a saturated aqueous solution of NaCl
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customto give a brown oil
  8. temperatureThe reaction was heated
  9. temperatureto reflux for 1.5 h
  10. temperatureIt was then cooled to 30° C.
  11. additionpoured onto ice (500 mL)
  12. customseparated
  13. washThe organic layer was washed with a saturated aqueous solution of NaCl
  14. dry with materialdried (MgSO4)
  15. customthe solvent removed in vacuo
  16. customto give a brown oil which
  17. customwas purified by column chromatography (Start 1:1 hexanes:acetone until product begins eluting, wash off with 95:5 acetone:MeOH)

Sources & evidence

ORD record
ord-e5620c4842144bcd81f9a682d5d02fa4
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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