3-Hydroxybenzaldehyde → (1RS,3RS)-1-(3-hydroxy-phenyl)-6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

HRID 41051Notes

Reaction equation

HRID 41051 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]([NH2:18])([CH3:17])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[NH:8][CH:7]=1.[OH:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH:24]=O.ClCCl>CO>[CH3:1][O:2][C:3]([C:4]1([CH3:17])[CH2:5][C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=3)[NH:8][C:7]=2[CH:24]([C:23]2[CH:26]=[CH:27][CH:28]=[C:21]([OH:20])[CH:22]=2)[NH:18]1)=[O:19]

Participants

5

Reactant 3

HCID 1013-HydroxybenzaldehydeHCID 6344DichloromethaneHCID 58212094(RS)-2-amino-3-(5-methoxy-1H-indol-3-yl)-2-methyl-propionic acid methyl ester2×

Product 1

HCID 68851536(1RS,3RS)-1-(3-hydroxy-phenyl)-6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl esterYield 15%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (+/−)-2-amino-3-(5-methoxy-1H-indol-3-yl)-2-methyl-propionic acid methyl ester (5.178 g, 19.5 mmol) and 3-hydroxybenzaldehyde (2.85 g, 23.4 mmol, 1.2 equiv.) in dry dichloromethane (80 ml) trifluoroacetic acid (1.5 ml, 19.5 mol, 1 equiv.) is added and the mixture is stirred under argon at room temperature. When TLC indicates the disappearance of (+/−)-2-amino-3-(5-methoxy-1H-indol-3-yl)-2-methyl-propionic acid methyl ester (1 day), a little methanol is added to dissolve the product precipitated during the reaction. The mixture is then diluted with dichloromethane (750 ml) and is washed with 2 M aqueous HCl, aqueous NaHCO3 and water, is dried and concentrated. Column chromatography (dichloromethane-ethyl acetate 9:17:1) of the residue gives 5.22 g (73%) of (1RS,3SR)-1-(3-hydroxy-phenyl)-6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester (m.p. 183-184° C. from ethyl acetate-light petroleum) and 1.07 g (15%) of (1RS,3RS)-1-(3-hydroxy-phenyl)-6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester (m.p. 175-177° C. from ethyl acetate-light petroleum).

Workup

  1. dissolutionto dissolve the product
  2. customprecipitated during the reaction
  3. additionThe mixture is then diluted with dichloromethane (750 ml)
  4. washis washed with 2 M aqueous HCl, aqueous NaHCO3 and water
  5. customis dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-daafb21c87154f1f9b9d7e80d8c22b63
Source dataset
uspto-grants-2013_09
Patent number
US08530493B2

Reaction notes

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