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

HRID 41052Notes

Reaction equation

HRID 41052 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]([NH2:19])([CH3:18])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:16][CH3:17])[CH:13]=2)[NH:8][CH:7]=1.[OH:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH:25]=O.FC(F)(F)C(O)=O.CO>ClCCl>[CH3:1][O:2][C:3]([C:4]1([CH3:18])[CH2:5][C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:16][CH3:17])[CH:13]=3)[NH:8][C:7]=2[CH:25]([C:24]2[CH:27]=[CH:28][CH:29]=[C:22]([OH:21])[CH:23]=2)[NH:19]1)=[O:20]

Participants

6

Reactant 4

HCID 1013-HydroxybenzaldehydeHCID 887MethanolHCID 6422Trifluoroacetic acidHCID 68851521(+/-)-2-amino-3-(5-ethoxy-1H-indol-3-yl)-2-methyl-propionic acid methyl ester

Product 1

HCID 68886227(1RS,3SR)-1-(3-hydroxy-phenyl)-6-ethoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (+/−)-2-amino-3-(5-ethoxy-1H-indol-3-yl)-2-methyl-propionic acid methyl ester (829 mg, 3 mmol), 3-hydroxybenzaldehyde (439 mg, 3.6 mmol) and trifluoroacetic acid (223 μl, 3 mmol) in dry dichloromethane (40 ml) is stirred for 6 h under argon. Methanol (2 ml) is added to dissolve the precipitated product and the mixture is diluted with dichloromethane (150 ml). It is washed with saturated aqueous NaHCO3 (2×50 ml) and water (2×50 ml), is dried, and the solvent is removed under reduced pressure. The residue is purified by column chromatography (dichloromethane-ethyl acetate, 7:1→4:1) to provide (1RS,3SR)-1-(3-hydroxy-phenyl)-6-ethoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester (1.05 g, 93%). M.p. 173-175° C. (from ethyl acetate-hexane).

Workup

  1. dissolutionto dissolve the precipitated product
  2. washIt is washed with saturated aqueous NaHCO3 (2×50 ml) and water (2×50 ml)
  3. customis dried
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is purified by column chromatography (dichloromethane-ethyl acetate, 7:1→4:1)

Sources & evidence

ORD record
ord-78674c6223224b03847f1c59fcb27478
Source dataset
uspto-grants-2013_09
Patent number
US08530493B2

Reaction notes

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