Hydrochloric Acid → (2R,4S)-4-Hydroxy-1-(2-Nitrophenyl) Proline

HRID 1976223Notes

Reaction equation

HRID 1976223 reaction equation
C[O:2][C:3](=[O:19])[C@H:4]1[CH2:8][C@@H:7]([OH:9])[CH2:6][N:5]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH-].[Na+].Cl>C(N(CC)CC)C.C(O)(=O)C.C1(C)C=CC=CC=1>[OH:9][C@@H:7]1[CH2:6][N:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N+:16]([O-:18])=[O:17])[C@@H:4]([C:3]([OH:19])=[O:2])[CH2:8]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 12042755(2R,4R)-4-Hydroxy-1-(2-Nitrophenyl) Proline Methyl Ester

Product 1

HCID 28157471(2R,4S)-4-Hydroxy-1-(2-Nitrophenyl) ProlineYield 74.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To 10 ml of anhydrous toluene, there were added 0.93 g of the (2R, 4R)-4-hydroxy-1-(2-nitrophenyl) proline methyl ester prepared in Reference Example 6, 1.8 g of triphenyl phosphine, 0.42 g of acetic acid and 0.25 g of triethylamine and then 1.4 g of diisopropyl azodicarboxylate was dropwise added to the resulting mixture over one hour with ice-cooling. After stirring the mixture for 16 hours with heating to 60° C. and cooling it to room temperature, 8 ml of a 1.3N sodium hydroxide solution was added to the mixture, followed by stirring the mixture for additional 4 hours at room temperature. The pH of the reaction solution was adjusted to 7 with concentrated hydrochloric acid, the insolubles precipitated were filtered off, the resulting filtrate was fractionated and the aqueous phase obtained was washed with ether. Then the aqueous phase was acidified with hydrochloric acid, followed by extraction with ethyl acetate, washing with water and drying over anhydrous magnesium sulfate. After concentration of the ethyl acetate extract, the resulting residue was recrystallized from ethyl acetate-chloroform to give 0.66 g (yield 74.8%) of the title compound.

Workup

  1. temperaturecooling
  2. temperaturecooling it to room temperature
  3. stirringby stirring the mixture for additional 4 hours at room temperature
  4. customthe insolubles precipitated
  5. filtrationwere filtered off
  6. customthe aqueous phase obtained
  7. washwas washed with ether
  8. extractionfollowed by extraction with ethyl acetate
  9. washwashing with water
  10. dry with materialdrying over anhydrous magnesium sulfate
  11. extractionAfter concentration of the ethyl acetate extract
  12. customthe resulting residue was recrystallized from ethyl acetate-chloroform

Sources & evidence

ORD record
ord-01a46bae77554eba9d21865b2618f364
Source dataset
uspto-grants-2001_05
Patent number
US06225306B1

Reaction notes

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