Acetic Acid → a-Methyltryptophan

HRID 233629

Reaction equation

HRID 233629 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH:11]=CC(NC(C(O)=O)C(O)=O)=O)=[CH:2]1.[CH3:23][CH2:24][OH:25].CC[O:28][C:29]([CH3:31])=[O:30].CC(O)=O.S(=O)(=O)(O)O.[N:41]1C=CC=CC=1.O>O>[C:24]([NH:41][CH:31]([CH:10]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1)[CH3:11])[C:29]([OH:28])=[O:30])(=[O:25])[CH3:23]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 21584252Ethanol ethylacetateHCID 54264913HCID 54264913, compoundHCID 66926435Pyridine water

Product 1

HCID 286539a-Methyltryptophan

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The malonic acid (73) (5.48 g, 18.0 mmol) was refluxed in pyridine/water (1:1) (20 mL) until no diacid remained (SiO2 :EtOH-EtOAc (1:1) +1% AcOH; rf 0.26). The reaction mixture was cooled, diluted with water (50 mL), and acidified with 10% sulphuric acid (50 mL). The resulting solution was left at 0° C. overnight to crystallize. The brown solid was filtered off and dried to yield 2-acetamido-3-(3-indolyl)butanoic acid isomer A (74A) (1.30 g, 28%); δ H (300M Hz; d6 -DMSO), 1.32 (3H, J 9 Hz, CH3), 1.84 (3H, s, CHH3CO), 3.46-3.55 (1H, m, indCH(CH3)-), 4.58-4.67 (1H, m, CH(COOH)NHAc), 6.93-7.19 (3H, m), 7.34 (1H, d, J 8 Hz, amide NH), 7.54 (1H, J 8 Hz, indole 7-H), 8.04 (1H, d, J 9 Hz, indole-4H), 10.81 (1H brs, indole NH), ca 12.4 (vbrs, CO2H). The filtrate was extracted with ethyl acetate (4×100 mL). The ethyl acetate extracts were combined and washed with water (2×50 mL) then extracted with 10% sodium hydrogen carbonate (2×100 mL). The sodium hydrogen carbonate extract was acidified with 4N sulphuric acid then extracted with ethyl acetate (2×75 mL). The ethyl acetate solution was washed with water (2×25 mL) then evaporated to dryness to give a beige foam, 2-acetamido-3-(3-indolyl)butanoic acid isomer B (74B) (2.17 g, 46%); δ H (300M Hz, d6 -DMSO), 1.32 (3H, d, J 7 Hz, CH3), 1.84 (3H, s, CH3CO), 3.50 (1H, M, ind CH(CH3)-), 4.66 (1H, m, CH(COOH)NHAc), 6.93-719 (3H, m), 7.34 (1H, d, J 8 Hz, amide NH), 7.63 (1H, d, J 8 Hz, indole 7-H), 7.84 (1H, d, J 9 Hz, indole 4-H), 10.83 (1H, s, indole NH), ca 12.5 (vbrs, CO2H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customto crystallize
  3. filtrationThe brown solid was filtered off
  4. customdried

Sources & evidence

ORD record
ord-4865f0a5b644496594a09b346d677a9d
Source dataset
uspto-grants-1997_01
Patent number
US05593967

Linked notes

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