Triethylamine → benzyl (1S,2S,4S)-4-[(tert-butoxycarbonyl)amino]-2-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamate

HRID 1174167Notes

Reaction equation

HRID 1174167 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:10][C@@H:11]1[O:15]C(C)(C)[N:13]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[C@H:12]1[CH2:28][C:29]1[CH:34]=[CH:33][C:32](OC(=O)C(F)(F)F)=[CH:31][CH:30]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[Cl-].C([Sn](CCCC)(CCCC)[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][N:57]=1)CCC.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>CN(C=O)C.C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:10][C@H:11]([OH:15])[C@@H:12]([NH:13][C:18](=[O:19])[O:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][N:57]=2)=[CH:31][CH:30]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 433294Lithium ChlorideHCID 6077842-(Tributylstannyl)pyridineHCID 67407042benzyl(4S,5S)-5-{(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}-2,2-dimethyl-4-{4-[(trifluoroacetyl)oxy]benzyl}-1,3-oxazolidine-3-carboxylate

Product 1

HCID 86726180benzyl (1S,2S,4S)-4-[(tert-butoxycarbonyl)amino]-2-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamateYield 25.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution containing the product from Example 23I (2.65 g, 3.75 mmol) in DMF (20 mL) was treated with LiCl (1.6 g, 37.74 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.5 g, 0.71 mmol), and 2-tri-n-butylstannylpyridine (2.6 mL, 11.30 mmol), heated at 100° C. for 16 hours, cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine and dried over MgSO4, filtered and concentrated. A solution of the residue in THF (30 mL) and aqueous HCl (30 mL, 1 N) was stirred at 50° C. for 48 hours, cooled to 0° C. and adjusted to pH 8 with 3 N NaOH solution. The reaction mixture was partitioned between ethyl acetate and water, and the organic phase was washed with brine and dried over MgSO4, filtered and concentrated. A solution of the residue in THF (30 mL) was treated with triethylamine (1 mL, 13.6 mmol) and di-tert-butyl dicarbonate (0.82 g, 3.75 mmol), stirred at 25° C. for 16 hours, and partitioned between ethyl acetate and saturated NaHCO3. The organic phase was washed with brine and dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane to give the title compound (0.568 g, 25% yield).

Workup

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. temperaturecooled to 0° C.
  8. customThe reaction mixture was partitioned between ethyl acetate and water
  9. washthe organic phase was washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. stirringstirred at 25° C. for 16 hours
  14. custompartitioned between ethyl acetate and saturated NaHCO3
  15. washThe organic phase was washed with brine
  16. dry with materialdried over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-e9d1cfba7ea645d783b80089d62caea6
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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