Acetic Acid → 3-Mercapto-2-(4-methoxy-benzylamino)-propionic acid

HRID 2219791

Reaction equation

HRID 2219791 reaction equation
[BH4-].[Na+].[OH-].[Na+].[CH3:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[NH:17][CH:16]([C:18]([OH:20])=[O:19])[CH2:15][S:14]2)=[CH:9][CH:8]=1.C(O)(=O)C>C([O-])([O-])=O.[K+].[K+]>[SH:14][CH2:15][CH:16]([NH:17][CH2:13][C:10]1[CH:9]=[CH:8][C:7]([O:6][CH3:5])=[CH:12][CH:11]=1)[C:18]([OH:20])=[O:19]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 28277282-(4-Methoxy-phenyl)-thiazolidine-4-carboxylic acidHCID 4311764Sodium borohydride2×

Product 1

HCID 110210473-Mercapto-2-(4-methoxy-benzylamino)-propionic acidYield 68.1%

Reagents, catalysts & solvents 1

HCID 11430Potassium CarbonateSolvent

Conditions

Temperature
2.5 °C

Procedure

A 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer was charged with sodium borohydride (221.3 g, 5.85 mol). A 1.75 L portion of 0.25 M sodium hydroxide was added and the mixture was stirred until homogeneous. The solution was cooled to 0-5° C. 2-(4-methoxyphenyl)-thiazolidine-4-carboxylic acid (350.0 g, 1.46 mol) was dissolved in 2.1 L of a 0.62 M K2CO3 aqueous solution. The resulting solution was added to the solution of sodium borohydride while maintaining an internal temperature of below 30° C. The reaction was stirred until HPLC analysis showed no remaining starting material (approximately 1 hour). The reaction was cooled to 0° C. and 700 mL of glacial acetic acid was added with stirring. The final pH of the reaction mixture was approximately 5. The resulting white solid was filtered, washed with 3 L of water and 2.5 L of ethanol, and dried in a vacuum oven at 50° C. for 12 hours. Approximately 240 g of 3-mercapto-2-(4-methoxy-benzylamino)-propionic acid was obtained (68% yield). 1H NMR (300 MHz, DMSO) δ 7.32 (d, 8.9 Hz, 2H), 6.91 (d, 8.9 Hz, 2H), 3.87 (AB, JAB=13.1 Hz, ΔvAB=18.5 Hz, 2H), 3.72 (s, 3H), 3.24 (dd, J=5.3, 5.3 Hz, 1H), 2.76 (d, J=5.7 Hz, 2H).

Workup

  1. customA 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer
  2. temperaturewhile maintaining an internal temperature of below 30° C
  3. stirringThe reaction was stirred until HPLC analysis
  4. customno remaining starting material (approximately 1 hour)
  5. temperatureThe reaction was cooled to 0° C.
  6. stirringwith stirring
  7. filtrationThe resulting white solid was filtered
  8. washwashed with 3 L of water and 2.5 L of ethanol
  9. customdried in a vacuum oven at 50° C. for 12 hours

Sources & evidence

ORD record
ord-877ef83902694cdb91d20fd89cd52a55
Source dataset
uspto-grants-2008_08
Patent number
US07414137B2

Linked notes

Loading…