Benzaldehyde → (2S)-2-(benzylamino)-3-hydroxypropanoic acid

HRID 895658Notes

Reaction equation

HRID 895658 reaction equation
[NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].[OH-].[Na+].[CH:10](=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[BH4-].[Na+]>C(OCC)C>[CH2:10]([NH:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 240Benzaldehyde2×HCID 5951L-SerineHCID 14798Sodium HydroxideHCID 4311764Sodium borohydride2×

Product 1

HCID 853606(2S)-2-(benzylamino)-3-hydroxypropanoic acidYield 40%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
5 °C

Procedure

A 5 L 3-neck round bottom flask was charged with L-serine (313 g, 3.0 mol) and 2N sodium hydroxide solution (1.5 L). Stirring was begun and benzaldehyde (322.4 g, 3.0 mol) added. After 15 minutes at room temperature the solution was cooled to 5° C. and sodium borohydride (35.0 g, 0.93 mol) was added in small portions so as to maintain the temperature below 10° C. Once the addition was complete the solution was allowed to warm to room temperature and stir for 2 h. At this point, a second portion of benzaldehyde (322.4 g, 3.0 mol) was added and the solution stirred for 15 minutes. The solution was cooled to 5° C. and sodium borohydride (35.0 g, 0.93 mol) added, again maintaining the temperature below 10° C. The reaction mixture was then warmed to room temperature and stirred for 2 h. Diethyl ether (1 L) was added, the solution stirred 5-10 minutes and the ether layer separated. The pH of the aqueous layer was then adjusted to 6 with 37% hydrochloric acid. Filtration of the resulting solids and recrystallization of the wet cake from water afforded 230 g (40%) of (S)-(+)-N-benzylserine after drying at 45° C. overnight.

Workup

  1. temperatureto maintain the temperature below 10° C
  2. additionOnce the addition
  3. temperatureto warm to room temperature
  4. stirringstir for 2 h
  5. stirringthe solution stirred for 15 minutes
  6. temperatureThe solution was cooled to 5° C.
  7. temperatureagain maintaining the temperature below 10° C
  8. temperatureThe reaction mixture was then warmed to room temperature
  9. stirringstirred for 2 h
  10. stirringthe solution stirred 5-10 minutes
  11. customthe ether layer separated
  12. filtrationFiltration of the resulting solids and recrystallization of the wet cake from water

Sources & evidence

ORD record
ord-4c80a188a448440abc061ae7211e0972
Source dataset
uspto-grants-2005_07
Patent number
US06916815B2

Reaction notes

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