Lithium Hydroxide → HCID 69137916, compound

HRID 451643Notes

Reaction equation

HRID 451643 reaction equation
C([O:5][C:6](=[O:34])[CH:7]([NH:17][C:18]([NH:20][CH:21]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([I:33])[CH:28]=1)[CH2:22][C:23]([O:25]C)=[O:24])=[O:19])[CH2:8][CH2:9][C:10]([O:12]C(C)(C)C)=[O:11])(C)(C)C.[Li+].[OH-].C(Cl)Cl.C(O)(C(F)(F)F)=O>CO.O>[C:23]([CH2:22][C@H:21]([NH:20][C:18](=[O:19])[NH:17][C@@H:7]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])[C:6]([OH:34])=[O:5])[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([I:33])[CH:28]=1)([OH:25])=[O:24]

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 69137399HCID 69137399, compound

Product 1

HCID 69137916HCID 69137916, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (±)2-{3-[1-(3-Iodo-phenyl)-2-methoxycarbonyl-ethyl]-ureido}-pentanedioic acid di-tert-butyl ester (289 mg, 0.49 mmol) was dissolved in methanol (3 mL) and 2M LiOH (0.5 mL) was added and the reaction stirred at room temperature overnight. The reaction was diluted with water (20 mL) and the organic layer was extracted with ethyl acetate (2×20 mL) then acidified with 1N HCl to pH ˜2. The aqueous layer was extracted with ethyl acetate (3×20 mL), dried over sodium sulfate and concentrated to afford the crude product (206 mg, 0.36 mmol, 73%) as a white solid. To the crude material was added DCM (2 mL) followed by TFA (2 mL) and the reaction was stirred at room temperature overnight. Concentration followed by recrystallization from ethyl acetate afforded the desired product (22 mg, 0.047 mmol, 10%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.39 (br, 3H), 7.64 (br, 1H), 7.56 (m, 1H), 7.30 (bm, 1H), 7.10 (bm, 1H), 6.72 (bm, 1H), 6.34 (bm, 1H), 4.94 (br, 1H), 4.03 (bm, 1H), 2.64 (br, 2H), 2.20 (br, 2H), 1.86 (br, 1H), 1.71 (br, 1H). ESMS m/z: 463 (M−H)+.

Workup

  1. extractionthe organic layer was extracted with ethyl acetate (2×20 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customto afford the crude product (206 mg, 0.36 mmol, 73%) as a white solid
  6. stirringthe reaction was stirred at room temperature overnight
  7. concentrationConcentration
  8. customfollowed by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-73f2c43685f94b8b84f81c7c4611792d
Source dataset
uspto-grants-2013_07
Patent number
US08487129B2

Reaction notes

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