Acetic Acid → 7-Fluorotryptophan

HRID 401604

Reaction equation

HRID 401604 reaction equation
C([O:3][C:4](=[O:25])[C:5]([CH2:14][C:15]1[C:23]2[C:18](=[C:19]([F:24])[CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)([NH:11]C=O)C(OCC)=O)C.[OH-].[Na+].C(O)(=O)C>C1COCC1>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]2[C:18]=1[NH:17][CH:16]=[C:15]2[CH2:14][C@@H:5]([C:4]([OH:25])=[O:3])[NH2:11]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 575633012-(7-Fluoro-1H-indol-3-ylmethyl)-2-formylamino-malonic acid diethyl ester

Product 1

HCID 159301487-FluorotryptophanYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(7-Fluoro-1H-indol-3-ylmethyl)-2-formylamino-malonic acid diethyl ester in THF was treated with NaOH (300 mg in 10 mL water) at room temperature for 24 hr. The mixture was slowly acidified with acetic acid (5 mL) and then refluxed for 24 hr. The reaction mixture was concentrated under vacuum, and treated with dil. HCl (10 mL, 3M) and then again refluxed for ˜16 h. The reaction was allowed to cool to room temperature. The pH was adjusted to 6.0 with 2M KOH. The white solid that formed was filtered, washed with water, and dried under vacuum to give 7-fluoro-tryptophan (282 mg, 52%): mp 256-261° C., 1H NMR (500 MHz, DMSO-d6): 2.92-2.97 (dd, J=8.5 and 15 Hz, 1H), 3.25-3.29 (dd, J=4.0 and 15 Hz, 1H), 3.38-3.41 (dd, J=4.0 and 8.5 Hz, 1H), 6.87-6.96 (m, 2H), 7.25 (s, 1H), 7.37 (d, J=7.5 Hz, 1H), 11.36 (s, 1H).

Workup

  1. temperaturerefluxed for 24 hr
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. additiontreated with dil. HCl (10 mL, 3M)
  4. temperatureagain refluxed for ˜16 h
  5. customThe white solid that formed
  6. filtrationwas filtered
  7. washwashed with water
  8. customdried under vacuum

Sources & evidence

ORD record
ord-00bd0c5c0620447892c414d223ac490b
Source dataset
uspto-grants-2014_06
Patent number
US08741942B2

Linked notes

Loading…