Sodium Thiosulfate Pentahydrate → HCID 54498398, compound

HRID 260875Notes

Reaction equation

HRID 260875 reaction equation
[C:1]([N:4]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C@@H:5]([CH2:13][OH:14])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([OH:3])=[O:2].[Br-].[Na+].Cl[O-].[Na+].C(=O)(O)[O-].[Na+].O.O.O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(OCC)(=O)C.C1(C)C=CC=CC=1.O.ClCCl>[C:1]([N:4]([CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C@@H:5]([CH:13]=[O:14])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([OH:3])=[O:2]

Participants

9

Reactant 5

HCID 61475Sodium Thiosulfate PentahydrateHCID 253881Sodium BromideHCID 516892Sodium BicarbonateHCID 23665760Sodium Hypochlorite2×HCID 67748062HCID 67748062, compound

Product 1

HCID 54498398HCID 54498398, compoundYield 90.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 6344DichloromethaneSolventHCID 21584019Toluene ethylacetateSolvent

Procedure

N-Carboxybenzyl-D-phenylalaninol (100 g ;0.35M) is dissolved in ethyl acetate/toluene (1:1; 1.5-2.0 L) or dichloromethane (1.0-2.0 L) and a solution of sodium bromide (18.0-25.2 g; 0.175-0.25M) in water (50-250 mL) added. The resulting two phase mixture is stirred and cooled to 0°-5° C. under a nitrogen atmosphere. 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical (TEMPO) (0.055-0.55 g; 3.5-35 mM) is added. A solution of buffered sodium hypochlorite, freshly prepared by dissolving sodium bicarbonate (10-25 g; 0.12-0.3M) and commercial sodium hypochlorite solution (6-12.5% w/w; 250-584 g; 0.42-0.49M) in water (25-250 g), is added over a period of one hour with fast agitation, maintaining the reaction temperature <5° C. A solution of sodium thiosulfate pentahydrate (21.8-122 g; 0.088-0.49M) in water (64 -370 mL) is then immediately added and the reaction mixture efficiently stirred until excess oxidants have been quenched as demonstrated by starch/iodide test. Agitation is stopped and the mixture allowed to settle at 5°-10° C. After 15 minutes, the phases are separated. The organic phase is then washed with aqueous sodium bicarbonate solution (3% w/w; 500 mL) and aqueous sodium chloride solution (3% w/w; 500 mL). The organic phase is concentrated by vacuum distillation to a volume of approximately 300 mL maintaining the heating bath <20° C. Heptane (750 mL) is added and the vacuum distillation optionally continued to precipitate the product, while maintaining the heating bath <20° C. The precipitate is filtered, washed with heptane (2×200 mL) and dried under vacuum at 20° C. to constant weight to yield N-carboxybenzyl-D-phenylalaninal (90 g; 90% yield) as a white crystalline solid.

Workup

  1. temperaturecooled to 0°-5° C. under a nitrogen atmosphere
  2. addition2,2,6,6-Tetramethyl-1-piperidinyloxy free radical (TEMPO) (0.055-0.55 g; 3.5-35 mM) is added
  3. additionis added over a period of one hour with fast agitation
  4. temperaturemaintaining the reaction temperature <5° C
  5. stirringthe reaction mixture efficiently stirred until excess oxidants
  6. customhave been quenched
  7. customto settle at 5°-10° C
  8. customthe phases are separated
  9. washThe organic phase is then washed with aqueous sodium bicarbonate solution (3% w/w; 500 mL) and aqueous sodium chloride solution (3% w/w; 500 mL)
  10. concentrationThe organic phase is concentrated by vacuum distillation to a volume of approximately 300 mL
  11. temperaturemaintaining the heating bath <20° C
  12. additionHeptane (750 mL) is added
  13. distillationthe vacuum distillation
  14. customto precipitate the product
  15. temperaturewhile maintaining the heating bath <20° C
  16. filtrationThe precipitate is filtered
  17. washwashed with heptane (2×200 mL)
  18. customdried under vacuum at 20° C. to constant weight

Sources & evidence

ORD record
ord-021efee6c89544f09a3c8f00b377a80a
Source dataset
uspto-grants-1996_06
Patent number
US05530124

Reaction notes

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