Tetrahydrofuran → 5'-((1R,2R)-1-Benzyl-2-ethoxycarbonyl-2-hydroxy-ethylcarbamoyl)-2'-fluoro-biphenyl-2-carboxylic Acid

HRID 2361129Notes

Reaction equation

HRID 2361129 reaction equation
C([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[C:18]([C:20](=[O:37])[NH:21][C@H:22]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C@H:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[OH:24])[CH:17]=[CH:16][C:15]=2[F:38])=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C1COCC1.[OH-].[Na+]>CCOC(C)=O>[CH2:30]([C@@H:22]([NH:21][C:20]([C:18]1[CH:17]=[CH:16][C:15]([F:38])=[C:14]([C:9]2[C:8]([C:6]([OH:7])=[O:5])=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:19]=1)=[O:37])[C@H:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[OH:24])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 21863450Trifluoroacetic acid methylene chlorideHCID 710736115'-((1R,2R)-1-Benzyl-2-ethoxycarbonyl-2-hydroxy-ethylcarbamoyl)-2'-fluoro-biphenyl-2-carboxylic acid t-butyl ester

Product 1

HCID 710738275'-((1R,2R)-1-Benzyl-2-ethoxycarbonyl-2-hydroxy-ethylcarbamoyl)-2'-fluoro-biphenyl-2-carboxylic AcidYield 99%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5′-((1R,2R)-1-benzyl-2-ethoxycarbonyl-2-hydroxy-ethylcarbamoyl)-2′-fluoro-biphenyl-2-carboxylic acid t-butyl ester (100 mg, 192 μmol, 1.0 eq.) was combined with 1:1 TFA/DCM (1 mL each) and stirred for 1 hour. The solvent was evaporated and THF (3 mL) and 1 M aqueous NaOH (577 μL, 3.0 eq.) were added. The mixture was stirred for 2 hours and EtOAc was added. The aqueous was extracted and the organic was washed with NaOH (0.2 mL), stirred, and the aqueous was extracted. The aqueous were acidified to pH ˜5 with concentrated HCl to yield a gummy solid. The aqueous was removed and the gummy solid was dissolved in AcOH and purified by preparative HPLC to yield the title compound (11.6 mg, 99% purity). MS m/z [M+H]+ calc'd for C26H24FNO6, 466.16. found 466.2.

Workup

  1. customThe solvent was evaporated
  2. stirringThe mixture was stirred for 2 hours
  3. extractionThe aqueous was extracted
  4. washthe organic was washed with NaOH (0.2 mL)
  5. stirringstirred
  6. extractionthe aqueous was extracted
  7. customto yield a gummy solid
  8. customThe aqueous was removed
  9. dissolutionthe gummy solid was dissolved in AcOH
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-91d055e593e348c7bad0b52aef8406c3
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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