Citric Acid → HCID 11492787, compound

HRID 594831Notes

Reaction equation

HRID 594831 reaction equation
[Li+].[Cl-].[Cl:3][C:4]([Cl:15])([Cl:14])[C@@H:5]1[N:9]2[CH2:10][CH2:11][CH2:12][C@H:8]2[C:7](=[O:13])[O:6]1.[Li+].CC([N-]C(C)C)C.[CH:24](OC)=[O:25].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[O:13]=[C:7]1[O:6][C@H:5]([C:4]([Cl:3])([Cl:14])[Cl:15])[N:9]2[CH2:10][CH2:11][CH2:12][C@@:8]12[CH:24]=[O:25]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 7865Methyl formateHCID 433294Lithium ChlorideHCID 2724682Lithium diisopropylamideHCID 10944680HCID 10944680, compound

Product 1

HCID 11492787HCID 11492787, compoundYield 66.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

After adding approximately 3.5 g LiCl bei −78° C. to a solution of 14.092 g (57.64 mmol, 1.0 eq) of the protected proline 103, 138 ml (86.46 mmol, 1.5 eq, 0.625 M) LDA in THF were dropped in over the course of 60 min. The solution was stirred for 30 min at this temperature, and then 15 ml (241.85 mmol, 4.0 eq) HCOOMe was very slowly dropped in over 120 min. The solution was stirred for another 30 min at −78° C., and then brought to a temperature of −40° C. over the course of 1 h. 120 ml of a 10% citric acid solution in water was then added, the substance was extracted 3× with 120 ml MTBE respectively, and the combined organic phases were washed with 500 ml saturated NaCl solution, dried over magnesium sulfate, and the solvent was removed under reduced pressure. Chromatography on silica gel with EtOAc/CyHex 1:4 as eluent yielded 10.388 g (38.12 mmol, 66%) of the product 104 as white solid.

Workup

  1. additionwere dropped in over the course of 60 min
  2. stirringThe solution was stirred for another 30 min at −78° C.
  3. custombrought to a temperature of −40° C. over the course of 1 h
  4. extractionthe substance was extracted 3× with 120 ml MTBE respectively
  5. washthe combined organic phases were washed with 500 ml saturated NaCl solution
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-9d069b97e3064a0aa724ddf5781b32ff
Source dataset
uspto-grants-2016_01
Patent number
US09242985B2

Reaction notes

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