Hydrochloric Acid → 1-(1-Hydroxypropyl)-indole-3-acetamide

HRID 617429Notes

Reaction equation

HRID 617429 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]#[N:12])=[CH:2]1.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][O:19]C(=O)C.Cl.[OH-:24].[K+]>CN(C=O)C.[Cl-].[Na+].O.O.CCOC(C)=O>[OH:19][CH:18]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([NH2:12])=[O:24])=[CH:2]1)[CH2:17][CH3:16]

Participants

10

Reactant 5

HCID 313Hydrochloric Acid2×HCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 351795Indole-3-acetonitrileHCID 122357751-Propanol, 3-bromo-, 1-acetate

Product 1

HCID 232889591-(1-Hydroxypropyl)-indole-3-acetamideYield 61.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent2×

Procedure

A solution of 3-indolylacetonitrile (3.00 g, 19.2 mmol) in DMF (30 mL) was added dropwise to a suspension of sodium hydride (1.08 g, 27.0 mmol) in DMF (10 mL) at room temperature. The resultant mixture was stirred at room temperature for 30 min. before a solution of 3-bromopropylacetate (4.87 g, 26.9 mmol) in DMF (15 mL) was added. The reaction was stirred an additional 3 hours at room temperature before being worked up extractively with EtOAc (250 mL), aqueous 0.5N HCl (200 mL), water (200 mL) and brine (50 mL) and the solvent was removed in vacuo to give 6.91 g (>100%) of crude alkylated product which was converted to 1-(1-hydroxypropyl)-indole-3-acetamide without purification as follows. The oil was dissolved in tert-butanol (70 mL), treated with freshly powdered potassium hydroxide (85%, 12.7 g, 192 mmol) and the resultant mixture heated to a gentle reflux for 1 hr. The reaction mixture was then poured into ice and the acidity adjusted to pH~1 using aqueous 6N HCl (35 mL). The reaction was worked up extractively using EtOAc (300 mL), water (200 mL), brine (50 ml) and the organic layer dried (MgSO4) and the solvent removed in vacuo to give a solid that was purified by flash chromatography using a 2:1 acetone:hexanes initially followed by 95:5 acetone:MeOH to give 2.73 g (61%) of 1-(1-Hydroxypropyl)-indole-3-acetamide. NMR. MS (FD) m/z=232 (M+, 100%). Analytical calculated for C13H16N2O2C, 67.22; H, 6.94; N, 12.06. Found C, 65.99; H. 7.24; N, 11.0.

Workup

  1. additionwas added
  2. customthe solvent was removed in vacuo
  3. customto give 6.91 g (>100%) of crude alkylated product which
  4. customwas converted to 1-(1-hydroxypropyl)-indole-3-acetamide without purification
  5. dissolutionThe oil was dissolved in tert-butanol (70 mL)
  6. temperaturea gentle reflux for 1 hr
  7. additionThe reaction mixture was then poured into ice
  8. dry with materialthe organic layer dried (MgSO4)
  9. customthe solvent removed in vacuo
  10. customto give a solid
  11. customthat was purified by flash chromatography

Sources & evidence

ORD record
ord-d0e609ce541943aaa83077037e131ecd
Source dataset
uspto-grants-1999_09
Patent number
US05948907

Reaction notes

Loading…