Benzaldehyde → (R)-2-(Benzylamino)-3-hydroxypropanoic acid

HRID 1366408Notes

Reaction equation

HRID 1366408 reaction equation
Cl.C[O:3][C:4](=[O:9])[C@@H:5]([CH2:7][OH:8])[NH2:6].C(N(CC)CC)C.[CH:17](=O)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[BH4-].[Na+].[OH-].[Na+].[OH-].[Na+].O.CO.Cl>CO.O>[C:18]1([CH2:17][NH:6][C@@H:5]([C:4]([OH:3])=[O:9])[CH2:7][OH:8])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

10

Reactant 7

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 11446470D-Serine methyl ester hydrochlorideHCID 86636928HCID 86636928, compound

Product 1

HCID 13543366(R)-2-(Benzylamino)-3-hydroxypropanoic acidYield 64.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent3×

Conditions

Temperature
10 °C

Procedure

As per the procedures of WO2005058245, a mixture of D-serine methyl ester hydrochloride (98.84 g, 635.3 mmol) in MeOH (280 mL) was cooled to 10° C. To the mixture was slowly added triethylamine (88.5 mL, 635.0 mmol). The mixture was warmed to room temperature and the resulting solution was cooled to 10° C. To the solution was added benzaldehyde (64 mL, 630.2 mmol), and the solution was stirred for 30 min. To the solution was added sodium borohydride (24.03 g, 635.2 mmol) portionwise over 30 min, and the mixture was stirred for a further 30 min. In a separate flask, MeOH (114 mL) was added to water (170 mL), and to this solution was added a solution of NaOH (77.25 g, 1931 mmol) in water (155 mL). The solution was cooled to 15° C., and the reductive amination mixture was slowly added to the NaOH-water-MeOH solution over 15 min. The solution was stirred and warmed to room temperature over 30 min, and water (170 mL) was added, followed by sufficient 6 N aqueous HCl to adjust the pH to 9.5. The solution was washed with EtOAc (2×60 mL), and sufficient 6 N aqueous HCl was added to adjust the pH to 6.5. The mixture was cooled to 0° C. and held overnight. The resulting solid was collected by vacuum filtration and washed with water (2×200 mL) followed by heptane (2×200 mL). The white solid was dried at 40° C. under high vacuum for 3 days to afford N-(phenylmethyl)-D-serine (79.51 g, 64%). LCMS: (M+H)+: 196.1.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. temperaturethe resulting solution was cooled to 10° C
  3. stirringthe mixture was stirred for a further 30 min
  4. temperatureThe solution was cooled to 15° C.
  5. stirringThe solution was stirred
  6. temperaturewarmed to room temperature over 30 min
  7. washThe solution was washed with EtOAc (2×60 mL), and sufficient 6 N aqueous HCl
  8. additionwas added
  9. temperatureThe mixture was cooled to 0° C.
  10. waitheld overnight
  11. filtrationThe resulting solid was collected by vacuum filtration
  12. washwashed with water (2×200 mL)
  13. customThe white solid was dried at 40° C. under high vacuum for 3 days

Sources & evidence

ORD record
ord-ce2a3d0a598d4a23958653b86788229f
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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