Formic Acid → (2R)-hydroxy-3-(o-nitrophenyl)propanoic acid

HRID 557480Notes

Reaction equation

HRID 557480 reaction equation
CC1C=CC(S(N[C@@H]([C@H](N)C2C=CC=CC=2)C2C=CC=CC=2)(=O)=O)=CC=1.[N+:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH2:36][C:37](=[O:41])[C:38]([OH:40])=[O:39])([O-:29])=[O:28].C(N(CC)CC)C.C(O)=O>C(N(CC)CC)C.CO>[OH:41][C@H:37]([CH2:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[N+:27]([O-:29])=[O:28])[C:38]([OH:40])=[O:39]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 795833-(2-Nitrophenyl)-2-oxopropanoic acidHCID 2734565N-((1R,2R)-2-Amino-1,2-diphenylethyl)-4-methylbenzene-1-sulfonamide

Product 1

HCID 13651759(2R)-hydroxy-3-(o-nitrophenyl)propanoic acidYield 133.2%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 887MethanolSolvent2×

Procedure

Into 120 ml of methanol were dissolved 293 mg (0.5 mmol) of [RuCl2(p-cymene)]2 and 360 mg (1.0 mmol) of (1R,2R)—N-tosyl-diphenylethylenediamine (hereinafter referred to as (R,R)-TsDPEN) to prepare a solution, and 0.27 ml (2.0 mmol) of triethylamine was dropwise added to the solution, followed by stirring for 0.5 hour at room temperature. To the reaction solution was dropwise added a solution prepared by dissolving 20 g (96 mmol) of o-nitrophenyl pyruvic acid into 80 ml of methanol, and 38.7 g (383 mmol) of triethylamine was furthermore dropwise added thereto. The bath was heated up to a temperature of 40° C., and then 13.2 g (278 mmol) of formic acid was dropwise added over 1 hour, followed by stirring for 2 hours at a bath temperature of 40° C. Upon completion of the reaction, the solvent was distilled off under reduced pressure. Thereto was added 40 ml of water, and then 22.6 g of concentrated hydrochloric acid was gradually dropwise added under ice cooling; thus, pH of the solution was adjusted to 2. Extraction was performed twice with 200 ml of ethyl acetate, and then the organic layer was washed with 20 ml of a saturated aqueous solution of sodium chloride, followed by concentration under reduced pressure. As a result, 27.0 g (yield 97%, 97% ee) of (2R)-hydroxy-3-(o-nitrophenyl)propanoic acid was obtained.

Workup

  1. additionwas dropwise added to the solution
  2. additionTo the reaction solution was dropwise added a solution
  3. customprepared
  4. additionwas furthermore dropwise added
  5. temperatureThe bath was heated up to a temperature of 40° C.
  6. stirringby stirring for 2 hours at a bath temperature of 40° C
  7. customUpon completion of the reaction
  8. distillationthe solvent was distilled off under reduced pressure
  9. additionThereto was added 40 ml of water
  10. addition22.6 g of concentrated hydrochloric acid was gradually dropwise added under ice cooling
  11. extractionExtraction
  12. washthe organic layer was washed with 20 ml of a saturated aqueous solution of sodium chloride
  13. concentrationfollowed by concentration under reduced pressure

Sources & evidence

ORD record
ord-46e0e230b6834585ace15702f0cef36b
Source dataset
uspto-grants-2011_11
Patent number
US08058471B2

Reaction notes

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