Water → 3-(5-Amino-4-ethylthio-3-indolyl)-1-propanol

HRID 441100Notes

Reaction equation

HRID 441100 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][CH2:15][OH:16])([O-])=O.[CH2:17]([SH:19])[CH3:18].[NH4+].[Cl-].O>CN(C=O)C.C1COCC1.CCOC(C)=O.[Zn]>[NH2:1][C:4]1[C:5]([S:19][CH2:17][CH3:18])=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][CH2:15][OH:16]

Participants

8

Reactant 4

HCID 962WaterHCID 6343EthanethiolHCID 25517Ammonium ChlorideHCID 199620365-Nitro-3-(3-hydroxypropyl)-1H-indole

Product 1

HCID 224056733-(5-Amino-4-ethylthio-3-indolyl)-1-propanolYield 20%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6228DimethylformamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

A cold (10°-12° C.) mixture of 3-(5-nitro-3-indolyl)-1-propanol (Example 3: 2.2 g, 10.0 mmol), ethanethiol (7.4 ml, 0.1 mol) and Zn dust (2.0 g, 30.6 mmol) in dry DMF (20 ml) kept under argon was treated portionwise with NH4Cl which was added at 10 min interval for 3 h while temperature of the mixture was kept between 10°-12° C. After the addition was completed, the reaction mixture was stirred for 3 h and then diluted with THF:EtOAc (1:2, 45 ml) mixture followed by slow addition of water (40 ml). The mixture was filtered on a glass fiber filter and the two phases separated. The aqueous phase was extracted with EtOAc: THF (2:1, 3×40 ml) mixture The organic extracts were combined, washed with water (2×50 ml), dried (MgSO4) and concentrated in vacuo. The crude material was chromatographed on silica gel dry column using first a mixture of CH2Cl2 : EtOAc (3:17) and then EtOAc both containing Et3N (0.5%). Appropriate fractions were concentrated in vacuo affording 3-(5-amino-4-ethylthio-3-indolyl)-1-propanol (0.50 g, 20%); 1H NMR (DMSO-d6) δ (ppm): 10.48 (s, 1H, indolic NH), 7.08 (d, J=8.5 Hz, 1H, indolic H-7), 6.94 (d, J=2.3 Hz, 1H, indolic H-2), 6.59 (d, J=8.5 Hz, indolic H-6), 4.88 (bs, 2H, NH2), 4.37 (t, J=5.1 Hz, 1H, OH), 3.4-3.6 (m, 2H, H-1), 2.9-3.1 (m, 2H, H-3), 2.65 (q, J=7.4 Hz, 2H, SCH2CH3), 1.7-1.9 (m, 2H, H-2), 1.09 (t, J=7.4 Hz, 3H, SCH2CH3); also isolated was 3-(5-amino-3-indolyl)-1-propanol (1.0 g, 55%); 1H NMR (DMSO-d6) δ (ppm): 10.2 (s, 1H, indolic NH), 7.00 (d, J=8.4 Hz, 1H, indolic H-7), 6.88 (dd, J=2.2 Hz, indolic H-2), 6.63 (d, J=2.0 Hz, indolic H-4), 6.44 (dd, J=8.4 Hz, J=2.0 Hz, 1H, indolic H-6), 4.4-4.6 (m, 3H, NH2 and OH), 3.3-3.5 (m, 2H, H-1), 2.5-2.7 (m, 2H, H-3), 1.6-1.9 (m, 2H, H-2).

Workup

  1. additionwas added at 10 min interval for 3 h while temperature of the mixture
  2. customwas kept between 10°-12° C
  3. additionAfter the addition
  4. filtrationThe mixture was filtered on a glass fiber
  5. filtrationfilter
  6. customthe two phases separated
  7. extractionThe aqueous phase was extracted with EtOAc: THF (2:1, 3×40 ml) mixture The organic extracts
  8. washwashed with water (2×50 ml)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe crude material was chromatographed on silica gel
  12. customdry column
  13. additiona mixture of CH2Cl2 : EtOAc (3:17)
  14. concentrationAppropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-7b3180c420f347d890591845272f3af0
Source dataset
uspto-grants-1996_05
Patent number
US05521188

Reaction notes

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