Hydrochloric Acid → (4R)-1-{[(3,5-dichlorophenyl)amino]carbonyl}-4-hydroxy-L-proline

HRID 1268760Notes

Reaction equation

HRID 1268760 reaction equation
[CH2:1]1[C@@H:5]([C:6]([OH:8])=[O:7])[NH:4][CH2:3][C@@H:2]1[OH:9].C([O-])([O-])=O.[K+].[K+].[Cl:16][C:17]1[CH:18]=[C:19]([N:24]=[C:25]=[O:26])[CH:20]=[C:21]([Cl:23])[CH:22]=1.Cl>O.C1COCC1>[Cl:16][C:17]1[CH:18]=[C:19]([NH:24][C:25]([N:4]2[CH2:3][C@H:2]([OH:9])[CH2:1][C@H:5]2[C:6]([OH:8])=[O:7])=[O:26])[CH:20]=[C:21]([Cl:23])[CH:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5810L-HydroxyprolineHCID 11430Potassium CarbonateHCID 944603,5-Dichlorophenyl isocyanate

Product 1

HCID 60073589(4R)-1-{[(3,5-dichlorophenyl)amino]carbonyl}-4-hydroxy-L-prolineYield 78.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a clear solution of L-trans-4-hydroxy-proline (10 g) (0.076 mol) and K2CO3 (15.7 g) (1.1 eq.) in 100 mL of water and 10 mL of THF, was added by portions 3,5-dichlorophenyl isocyanate (15.7 g) (1.1 eq.). The white suspension was stirred at RT overnight. The aqueous mixture was acidified with conc. HCl, ,then extracted with EtOAc. The organic extracts were combined, washed with water, dried over MgSO4, filtered, and the solvent removed in vacuo to afford the titled compound (19 g) (yield 78.5%). 1H NMR (DMSOd6): 8.7 (1H,COOH), 7.65 (2H,d), 7.1 (1H,m), 5.2 (1H,NH), 4.4 (2H,m), 3.6 (1H,dd), 3.45 (1H,d), 2.1–2.25 (1H, m), 1.85–2.05 (1H,m).

Workup

  1. extractionextracted with EtOAc
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-3150bd79e7954965aebf4000c636840d
Source dataset
uspto-grants-2007_04
Patent number
US07199125B2

Reaction notes

Loading…