Sodium Hydroxide → 3-Mercapto-2-(4-methoxy-benzylamino)-propionic acid

HRID 551771

Reaction equation

HRID 551771 reaction equation
[SH:1][CH2:2][C@H:3]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[C:4]([OH:6])=[O:5].[BH4-].[Na+].[OH-].[Na+].COC1C=CC(C2NC(C(O)=O)CS2)=CC=1>C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>[SH:1][CH2:2][CH:3]([NH:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)[C:4]([OH:6])=[O:5]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 28277282-(4-Methoxy-phenyl)-thiazolidine-4-carboxylic acidHCID 4311764Sodium borohydride2×HCID 13891591(R)-3-Mercapto-2-(4-methoxybenzylamino)propanoic Acid

Product 1

HCID 110210473-Mercapto-2-(4-methoxy-benzylamino)-propionic acidYield 68%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
2.5 °C

Procedure

Preparation of (R)-3-mercapto-2-(4-methoxy-benzylamino)-propionic acid (A compound of Formula IIa): 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-methoxy-phenyl)-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, ΔνAB=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. customfitted 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-ced44baabcfd4a6f8f72164352b7cc49
Source dataset
uspto-grants-2011_05
Patent number
US07947850B2

Linked notes

Loading…