Hydrochloric Acid → HCID 57947438, compound

HRID 340925Notes

Reaction equation

HRID 340925 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([O:13][CH2:14][C@@H:15]([N:22]([CH3:35])[C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[Cl:34])=[O:24])[CH2:16][CH2:17][C:18]([O:20]C)=[O:19])=[O:12].[Li+].[OH-].Cl.C(OCC)(=O)C>O1CCOCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([O:13][CH2:14][C@@H:15]([N:22]([CH3:35])[C:23]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[Cl:34])=[O:24])[CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[O:12]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8857Ethyl AcetateHCID 57947351HCID 57947351, compound

Product 1

HCID 57947438HCID 57947438, compoundYield 0.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-methyl 5-(benzo[d]thiazol-2-ylcarbamoyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoate (2.3 g, 4.4 mmol) in 1,4-dioxane (15 mL) was added LiOH (2 N, 4.4 mL, 2 equiv.). The reaction mixture was stirred at RT for 2 h. The mixture was acidified to pH ˜3 with HCl (1 N, ˜10 mL), and ethyl acetate (50 mL) was added. The organic layer was extracted with EtOAc (3×20 mL), dried over Na2SO4 and concentrated. A small sample (30 mg) was purified by RP-HPLC (20-100% ACN in H2O) to give (S)-5-(benzo[d]thiazol-2-ylcarbamoyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoic acid as a white solid (8 mg). The remainder was used without further purification. LRMS (M−H+)=507.4.

Workup

  1. additionwas added
  2. extractionThe organic layer was extracted with EtOAc (3×20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customA small sample (30 mg) was purified by RP-HPLC (20-100% ACN in H2O)

Sources & evidence

ORD record
ord-52a427bfcf2648d08e651ae098cac30b
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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