Hydrochloric Acid → (4S,5S)-2-(4-bromobenzyl)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-6-phenylhexanoic Acid

HRID 1174263Notes

Reaction equation

HRID 1174263 reaction equation
[Br:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][CH:7]2[C:11](=[O:12])[O:10][C@H:9]([C@@H:13]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:8]2)=[CH:4][CH:3]=1.[OH-:31].[Na+].Cl.N1C=CN=C1.[Si:39](Cl)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40]>O1CCOCC1>[Br:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][CH:7]([CH2:8][C@H:9]([O:31][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[C@@H:13]([NH:21][C:22]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:28])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([OH:10])=[O:12])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 14798Sodium HydroxideHCID 28928tert-Butyldimethylsilyl chlorideHCID 86598818tert-butyl (1S)-1-[(2S)-4-(4-bromobenzyl)-5-oxotetrahydro-2-furanyl]-2-phenylethylcarbamate

Product 1

HCID 67408601(4S,5S)-2-(4-bromobenzyl)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-6-phenylhexanoic AcidYield 60%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution containing the product from Example 92B (18.4 g) in dioxane (190 mL) was treated with sodium hydroxide solution (45 mL, 1N) for 1 hour at 25° C. The mixture was cooled to 0° C., and acidified to pH 5 using 4N HCl, and concentrated under reduced pressure. The concentrate was partitioned between chloroform and water. The organic phase layer was washed with brine, dried over MgSO4, and concentrated. A solution of the residue (22 g) in dioxane (115 mL) was treated with imidazole (19 g, 279 mmol) and t-butyldimethylsilyl chloride (35 g, 232 mmol), stirred at 25° C. for 18 hours and concentrated. The residue was combined with ice, acidified with 4N HCl to pH 3, and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4, filtered, and concentrated. A solution of the residue in a mixture of THF (180 mL), acetic acid (180 mL), and water (60 mL) was stirred for 1 hour at 25° C. and concentrated. The residue was chromatographed on silica gel eluting with 0-50% ethyl acetate in chloroform to give the title compound (14.18 g, 60% yield).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe concentrate was partitioned between chloroform and water
  3. washThe organic phase layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. concentrationconcentrated
  7. extractionextracted with ethyl acetate
  8. washThe organic phase was washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. additionA solution of the residue in a mixture of THF (180 mL), acetic acid (180 mL), and water (60 mL)
  13. stirringwas stirred for 1 hour at 25° C.
  14. concentrationconcentrated
  15. customThe residue was chromatographed on silica gel eluting with 0-50% ethyl acetate in chloroform

Sources & evidence

ORD record
ord-849ef686fd5040b7ac61285481f2e54b
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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