Citric Acid → HCID 59659329, compound

HRID 2056646Notes

Reaction equation

HRID 2056646 reaction equation
[OH-:1].[Li+].OO.C([C@H]1COC(=O)N1[C:18](=[O:57])[C@H:19]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([N:46]([C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[CH2:47][CH:48]([CH3:50])[CH3:49])[CH:39]=1)[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=O)[C:29]2[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:36])=[CH:23][CH:22]=1)C1C=CC=CC=1.S([O-])(O)=[O:59].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[Cl:36][C:30]1[CH:31]=[CH:32][CH:33]=[C:34]([Cl:35])[C:29]=1[C:28]([NH:27][C:24]1[CH:23]=[CH:22][C:21]([CH2:20][C@@H:19]([C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([N:46]([C:51](=[O:56])[C:52]([CH3:53])([CH3:54])[CH3:55])[CH2:47][CH:48]([CH3:50])[CH3:49])[CH:39]=2)[C:18]([OH:59])=[O:57])=[CH:26][CH:25]=1)=[O:1]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 23665763Sodium BisulfiteHCID 69307713HCID 69307713, compound

Product 1

HCID 59659329HCID 59659329, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixed solvent of tetrahydrofuran (60 mL) and distilled water (20 mL) was added with a 2 mol/L aqueous lithium hydroxide solution (4.5 mL, 8.8 mmol) and 30 wt % of hydrogen peroxide (3.9 mL, 35.2 mmol) at 0° C., and the mixture was further added with a tetrahydrofuran (30 mL) solution of N-[4-(3-(4(S)-benzyl-oxooxazolidine-3-yl)-2(S)-{3-[(2,2-dimethylpropionyl)isobutylamino]-4-methoxyphenyl}-3-oxopropyl)phenyl]-2,6-dichlorobenzamide (3.3 g, 4.4 mmol), and was then stirred for 30 minutes. After the reaction, the solution was added with a saturated aqueous sodium hydrogen sulfite solution (42 mL) and a 10 wt % aqueous citric acid solution (33 mL), stirred for 30 minutes, extracted with ethyl acetate (100 mL×2), and the extract was dried over anhydrous magnesium sulfate. The dried organic phase was filtered, the filtrate was concentrated under reduced pressure, and the resultant residue was purified through silica gel column chromatography (n-hexane:ethyl acetate (v/v)=2:1) to thereby obtain 3-[4-(2,6-dichlorobenzoyl amino)phenyl]-2(S)-{3-[(2,2-dimethylpropionyl)isobutyl amino]-4-methoxyphenyl}propionic acid (yield: 1.3 g, yield ratio: 50%).

Workup

  1. distillationA mixed solvent of tetrahydrofuran (60 mL) and distilled water (20 mL)
  2. customAfter the reaction
  3. extractionextracted with ethyl acetate (100 mL×2)
  4. dry with materialthe extract was dried over anhydrous magnesium sulfate
  5. filtrationThe dried organic phase was filtered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe resultant residue was purified through silica gel column chromatography (n-hexane:ethyl acetate (v/v)=2:1) to thereby obtain 3-[4-(2,6-dichlorobenzoyl amino)phenyl]-2(S)-{3-[(2,2-dimethylpropionyl)isobutyl amino]-4-methoxyphenyl}propionic acid (yield: 1.3 g, yield ratio: 50%)

Sources & evidence

ORD record
ord-2380ca42cdb544eea4cd889c5e490dcf
Source dataset
uspto-grants-2008_02
Patent number
US07335673B2

Reaction notes

Loading…