L-Tryptophan → Methyl tryptophanate hydrochloride

HRID 589263Notes

Reaction equation

HRID 589263 reaction equation
[C:1]([Cl:4])(=O)C.[NH2:5][C@H:6]([C:17]([OH:19])=[O:18])[CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1>CO>[ClH:4].[CH3:1][O:18][C:17](=[O:19])[C@H:6]([CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)[NH2:5]

Participants

4

Reactant 2

HCID 6305L-TryptophanHCID 6367Acetyl chloride

Product 1

HCID 2734891Methyl tryptophanate hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Anhydrous methanol (50 mL) is taken in a 100 mL 2-necked round bottom flask fitted with a reflux condenser and an additional dropping funnel and cooled to ice temperature. Acetylchloride (3 mL) is added drop wise through the dropping funnel. After 15 min, L-tryptophan (3 g) is added and the reaction mixture is refluxed at 70° C. for 6 h. The reaction mixture is vacuo dried to obtain L-tryptophan methyl ester hydrochloride in quantitative yield and used for further reaction without purification. 1,4,5,8-Naphthalenetetracarboxylic dianhydride (200 mg, 0.746 mmol) and L-tryptophan methyl ester hydrochloride (380 mg 1.491 mmol) are suspended in 20 mL of DMF in a 100 mL round bottom flask. To this suspension is added 0.5 mL of triethylamine under inert atmosphere. The reaction mixture is refluxed at 65° C. for 21 h. Solvent is evaporated under vacuo and the residue is purified by column chromatography (15% methanol in chloroform) to obtain NDI 2 in good yield. Yield 86%. 1H NMR: (400 MHz, CDCl3-CF3COOH) δppm 3.64-3.70, (dd, 2H, CH2, J=8 Hz, 8 Hz); 3.78-3.84, (dd, 2H, CH2, J=8 Hz, 8 Hz); 3.90 (s, 6H, CH3); 6.12-6.16 (dd, 2H, αCH, J=8 Hz, 4 Hz); 6.86-7.02 (m, 6H, ArH); 7.13-7.15 (d, 2H, ArH, J=8 Hz); 7.46-7.48 (d, 2H, ArH, J=8 Hz); 8.57 (s, 4H, ArH). 13C NMR: (400 MHz, CDCl3-CF3COOH) δppm 24.5, 53.9, 55.1, 110.2, 110.4, 118.6, 119.8, 122.4, 123.2, 126.1, 126.6, 127.2, 131.8, 136.1, 163.0, 172.5. MS (EI): m/z=668.19[M]+ for C33H23N4O3. Elemental analysis: Found: C, 68.23; H, 4.25; N, 8.35; Calcd: C, 68.26; H, 4.22; N, 8.38 for C33H23N4O3.

Workup

  1. customfitted with a reflux condenser and an additional dropping funnel
  2. temperaturecooled to ice temperature
  3. customdried

Sources & evidence

ORD record
ord-a29d6059d8954e88bb7796ad778f7c91
Source dataset
uspto-grants-2016_01
Patent number
US09230708B2

Reaction notes

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