L-Hydroxyproline → trans-4-Hydroxy-1-(4-nitrobenzyloxycarbonyl)-L-proline

HRID 1194940Notes

Reaction equation

HRID 1194940 reaction equation
[OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.[OH-:10].[Na+].[CH:12]1[C:17]([CH2:18][Cl-]C([O-])=O)=[CH:16][CH:15]=[C:14]([N+:23]([O-:25])=[O:24])[CH:13]=1.[O:26]1[CH2:31]COCC1>O>[OH:1][C@H:2]1[CH2:6][N:5]([C:31]([O:26][CH2:18][C:17]2[CH:12]=[CH:13][C:14]([N+:23]([O-:25])=[O:24])=[CH:15][CH:16]=2)=[O:10])[C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1

Participants

6

Reactant 4

HCID 5810L-HydroxyprolineHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 178525823HCID 178525823, compound

Product 1

HCID 10566895trans-4-Hydroxy-1-(4-nitrobenzyloxycarbonyl)-L-prolineYield 70%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

(2S,4R)-(-)-4-Hydroxy-2-pyrrolidinecarboxylic acid [trans-4-hydroxy-L-proline](5.24 g, 40 mmol) in water (40 ml) was treated with 1M aqueous sodium hydroxide (40 ml), cooled in an ice-bath and then treated with 4-nitrobenzylchloroformate (8.64 g, 40 mmol) in 1,4-dioxane (40 ml), added dropwise over 20 min. The mixture was stirred at 0° C. for 3 h. Most of the 1,4-dioxane was removed by evaporation under reduced pressure and ethyl acetate (100 ml) and water (100 ml) were added. The mixture was acidified and the aqueous layer extracted a further two times with ethyl acetate (100 ml). The ethyl acetate layer was dried (MgSO4) and evaporated under reduced pressure to leave an oil which crystallised after trituration under diethyl ether. The crystals were filtered off to give the title compound (8.69 g, 70%) as a mixture of conformers/rotamers, m.p. 136°-137° C. (EtOAc/hexane) (Found: C, 50.30; H, 4.43; N, 8.82 C13H14N2O7 requires C, 50.32; H, 4.55; N, 9.03%); [α]D -38° (c 1 in EtOH); νmax (KBr) 3319, 1737, 1663, 1607, 1518, 1456, and 1342 cm-1 ; δH (250 MHz, (CD3)2CO) 2.20-2.25 (1H, m), 2.25-2.50 (1H, m), 3.50-3.72 (2H, m), 4.4-4.6 (2H, m), 5.18 (d, J 14.2 Hz), 5.29 (s), 5.33 (d, J 14.2 Hz) (together 2H, OCH2Ar, 2 conformers ), 7.66 (2H, m), and 8.23 (2H, m); [Mass spectrum M+ (310)].

Workup

  1. temperaturecooled in an ice-bath
  2. additionadded dropwise over 20 min
  3. customMost of the 1,4-dioxane was removed by evaporation under reduced pressure and ethyl acetate (100 ml) and water (100 ml)
  4. additionwere added
  5. extractionthe aqueous layer extracted a further two times with ethyl acetate (100 ml)
  6. dry with materialThe ethyl acetate layer was dried (MgSO4)
  7. customevaporated under reduced pressure
  8. customto leave an oil which
  9. customcrystallised after trituration under diethyl ether
  10. filtrationThe crystals were filtered off

Sources & evidence

ORD record
ord-8e7b94c8bf324c189a8771370a684254
Source dataset
uspto-grants-1989_03
Patent number
US04816452

Reaction notes

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