1H-Indole-3-propanoic acid → 3-{[3-(1H-Indol-3-yl)-propylamino]methyl}-2,3-dihydro-benzo[1,4]dioxin-6-ol

HRID 1290264Notes

Reaction equation

HRID 1290264 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][C:12](O)=O)=[CH:2]1.O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C.Cl.[OH:36][C:37]1[CH:38]=[CH:39][C:40]2[O:45][CH2:44][C@H:43]([CH2:46][NH2:47])[O:42][C:41]=2[CH:48]=1>CN(C=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][NH:47][CH2:46][CH:43]2[CH2:44][O:45][C:40]3[CH:39]=[CH:38][C:37]([OH:36])=[CH:48][C:41]=3[O:42]2)=[CH:2]1

Participants

6

Reactant 4

HCID 37441H-Indole-3-propanoic acidHCID 12734DiisopropylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 70201470(S)-7-hydroxy-2,3-dihydro-1,4-benzodioxin-2-methanamine hydrochloride

Product 1

HCID 189239073-{[3-(1H-Indol-3-yl)-propylamino]methyl}-2,3-dihydro-benzo[1,4]dioxin-6-olYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-Indolepropionic acid (1.4 g, 7.4 mmole), 1-hydroxybenzotriazole hydrate (1.2 g, 8.9 mmole) and 1,3-diisopropylcarbodiimide (2.8 ml, 17.8 mmole) were combined in 100 ml of DMF and stirred at room temperature for 2 hours under a nitrogen atmosphere. To this was added dropwise (S)-7-hydroxy-2,3-dihydro-1,4-benzodioxin-2-methanamine hydrochloride (1.6 g, 7.4 mmole) in 50 ml of DMF and the mixture was further stirred for 24 hours. The solvent was removed and the residue partitioned between dichloromethane and water. The separated dichloromethane layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue was chromatographed on a silica gel column using ethyl acetate as the eluant. Fractions containing product were concentrated and washed with a minimum amount of THF to remove a by-product and to give 1.5 g (60%) of the desired product, (S)-(7-hydroxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-4-(1H-indol-3-yl)-propanamide, as a white fluffy solid.

Workup

  1. stirringthe mixture was further stirred for 24 hours
  2. customThe solvent was removed
  3. customthe residue partitioned between dichloromethane and water
  4. dry with materialThe separated dichloromethane layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customThe residue was chromatographed on a silica gel column
  8. additionFractions containing product
  9. concentrationwere concentrated
  10. washwashed with a minimum amount of THF
  11. customto remove a by-product

Sources & evidence

ORD record
ord-1bfd5189aac845a7a1bef9e5bf737d92
Source dataset
uspto-grants-1998_05
Patent number
US05750724

Reaction notes

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