Citric Acid → HCID 10224048, compound

HRID 2182922Notes

Reaction equation

HRID 2182922 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([N:22]3[CH2:25][CH:24]([C:26]([O:28][CH3:29])=[O:27])[CH2:23]3)=[O:21])[N:16]=2)[CH2:11][C:12](O)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.ClC(OCC(C)C)=O.C[Si](C)(C)[O:47][NH2:48].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.O>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([N:22]3[CH2:25][CH:24]([C:26]([O:28][CH3:29])=[O:27])[CH2:23]3)=[O:21])[N:16]=2)[CH2:11][C:12]([NH:48][OH:47])=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 23378032HCID 23378032, compound

Product 1

HCID 10224048HCID 10224048, compoundYield 72.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (3R)-6-cyclohexyl-3-(3-{[3-(methoxycarbonyl)-1-azetidinyl]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoic acid (Preparation 43) (200 mg, 0.49 mmol) and N-methylmorpholine (59 μl, 0.54 mmol) in anhydrous dichloromethane (7 ml) was cooled to 0° C., treated with isobutyl chloroformate (70 μl, 0.54 mmol) and stirred under a nitrogen atmosphere for 1 hour. O-(Trimethylsilyl)hydroxylamine (175 μl, 1.47 mmol) was added and the mixture was for 18 hours, being allowed to warm to room temperature over this time. The mixture was then treated with aqueous citric acid solution (10% w/v, 10 ml) and stirred for 2 hours. This mixture was then diluted with water and extracted with ethyl acetate (×3). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by HPLC to afford the title compound as a foam (150 mg).

Workup

  1. waitthe mixture was for 18 hours
  2. stirringstirred for 2 hours
  3. extractionextracted with ethyl acetate (×3)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-35092dc497ea4018a5bbdb2c5415b2dd
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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