Citric Acid → HCID 59131023, compound

HRID 1992668Notes

Reaction equation

HRID 1992668 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:9]=1[CH:10]=[CH:11][C:12]([OH:14])=O.[OH-].[Na+].[Cl-].[Li+].C(N(CC)CC)C.[CH2:31]([C@H:38]1[CH2:42][O:41][C:40](=[O:43])[NH:39]1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.CN(C)C=O>[CH2:31]([C@H:38]1[CH2:42][O:41][C:40](=[O:43])[N:39]1[C:12](=[O:14])/[CH:11]=[CH:10]/[C:9]1[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:8]=1[F:7])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

10

Reactant 7

HCID 311Citric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 433294Lithium ChlorideHCID 6035023-(2,4-Difluorophenyl)acrylic AcidHCID 736225(S)-4-Benzyl-2-oxazolidinone

Product 1

HCID 59131023HCID 59131023, compoundYield 87.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent5×

Procedure

Oxalyl chloride (19 mL, 216 mmol) in dichloromethane (50 mL) was added dropwise to an ice-cooled stirred suspension of 2,4-difluorocinnamic acid (20.0 g, 108 mmol) in dichloromethane (400 mL) and N,N-dimethylformamide (0.4 mL) over 0.5 hours (waste gases from the reaction were scrubbed with a solution of concentrated sodium hydroxide). Once addition was complete, the reaction mixture was allowed to warm up to room temperature and was stirred at room temperature under nitrogen for 18 hours. The reaction mixture was then concentrated and azeotroped with dichloromethane (2×50 mL). The resulting acid chloride was redissolved in dichloromethane (50 mL) and this solution was added dropwise under nitrogen to a vigorously stirred suspension of lithium chloride (23.0 g, 540 mmol), triethylamine (76 mL, 540 mol) and (S)-(−)-4-benzyl-2-oxazolidinone (18.3 g, 103 mmol) in dichloromethane (400 mL) over 30 minutes. Once addition was complete, the reaction mixture was stirred at room temperature under nitrogen for 2.5 hours. The reaction mixture was diluted with dichloromethane (200 mL) and treated with a solution of 5% citric acid solution (500 mL). The organic layer was then separated and dried over magnesium sulfate. Filtration and evaporation of the dichloromethane gave the crude product as an orange oil. The crude material was redissolved in dichloromethane (100 mL) and the resulting solution was passed through a plug of silica, eluting with dichloromethane. The filtrate (1 L) was finally concentrated to afford 30.8 g of the product as a white solid.

Workup

  1. temperaturecooled
  2. additionOnce addition
  3. stirringwas stirred at room temperature under nitrogen for 18 hours
  4. concentrationThe reaction mixture was then concentrated
  5. customazeotroped with dichloromethane (2×50 mL)
  6. dissolutionThe resulting acid chloride was redissolved in dichloromethane (50 mL)
  7. additionOnce addition
  8. stirringthe reaction mixture was stirred at room temperature under nitrogen for 2.5 hours
  9. customThe organic layer was then separated
  10. dry with materialdried over magnesium sulfate
  11. filtrationFiltration and evaporation of the dichloromethane
  12. customgave the crude product as an orange oil
  13. washeluting with dichloromethane
  14. concentrationThe filtrate (1 L) was finally concentrated

Sources & evidence

ORD record
ord-42b591a714474ed3b1d8eb3f725dbbda
Source dataset
uspto-grants-2010_01
Patent number
US07649002B2

Reaction notes

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