Benzyl Alcohol → benzyl (2S)-2-aminopropanoate

HRID 1835590Notes

Reaction equation

HRID 1835590 reaction equation
S(Cl)(Cl)=O.[NH2:5][C@H:6]([C:8]([OH:10])=[O:9])[CH3:7].[CH2:11](O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([O:9][C:8](=[O:10])[C@H:6]([CH3:7])[NH2:5])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

4

Reactant 3

HCID 244Benzyl AlcoholHCID 5950L-AlanineHCID 24386Thionyl Chloride

Product 1

HCID 726858benzyl (2S)-2-aminopropanoateYield 67%

Conditions

Temperature
-10 °C

Procedure

Thionylchloride (9.8 ml, 135 mmol, 1.2 eqv) was added dropwise during 15 min. to benzyl alcohol (210 ml) stirred under nitrogen and cooled to −10° C. Alanine (10.0 g, 112 mmol, 1.0 eqv) was added in portions during 10 min. The reaction mixture was heated overnight at 60-70° C. The reaction mixture was evaporated in vacuo and the residue was dissolved in water (150 ml). The pH was adjusted to 1-2 by addition of 4N HCl (aq.) and the aqueous phase was extracted with dichloromethane (2×200 ml). The organic phase was washed with hydrochloric acid (pH 1, 1×50 ml). The aqueous phases were collected, alkalinized (to pH 9-10) by addition of 2N NaOH (aq.) and subsequently extracted with dichloromethane (2×200 ml and 1×100 ml—alkaline extract). The alkaline extract was dried (Na2SO4), filtered and evaporated under reduced pressure affording 13.39 g (67%) of the title compound as a colorless oil. The product was characterized as its hydrochloride: The product (0.50 g, 2.8 mmol) was dissolved in ether (5 ml) and HCl in ether (2 ml) was added. The precipitate was collected by filtration and washed with ether (2×5 ml) yielding 0.57 g (95%) of white crystalline alanine benzyl ester hydrochloride. 1H-NMR (D2O/TMS): δ 1.48 (unresolved d, 3H, Me); 4.15 (unresolved q, 1H, CH); 5.20 (s, 2H, CH2); 7.38 (br s, 5H, Ph). 13C-NMR (D2O/TMS): δ 14.7 (Me); 48.4 (CH); 68.1 (CH2); 128.1, 128.5, 134.3 (Ph); 170.1 (C═O). MS(FAB+) m/z (%): 180 (100, M-HCl+H). Anal. Calcd. for C10H14,ClNO2: C, 55.69; H, 6.54; N, 6.49. Found: C, 55.60; H, 6.56; N, 6.40.

Workup

  1. temperatureThe reaction mixture was heated overnight at 60-70° C
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionthe residue was dissolved in water (150 ml)
  4. additionThe pH was adjusted to 1-2 by addition of 4N HCl (aq.)
  5. extractionthe aqueous phase was extracted with dichloromethane (2×200 ml)
  6. washThe organic phase was washed with hydrochloric acid (pH 1, 1×50 ml)
  7. customThe aqueous phases were collected
  8. additionby addition of 2N NaOH (aq.)
  9. extractionsubsequently extracted with dichloromethane (2×200 ml and 1×100 ml—alkaline extract)
  10. extractionThe alkaline extract
  11. dry with materialwas dried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-2b3cab0fb1a94fe58a2e2d52a404decb
Source dataset
uspto-grants-2004_08
Patent number
US06770738B1

Reaction notes

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