Pyridine → HCID 125497801, compound

HRID 578651Notes

Reaction equation

HRID 578651 reaction equation
[S:1](Cl)(Cl)=[O:2].[C:5]([O:9][C:10](=[O:22])[NH:11][C@@H:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=1)[CH2:13][OH:14])([CH3:8])([CH3:7])[CH3:6].N1C=CC=CC=1.I([O-])(=O)(=O)=[O:30].[Na+]>C(#N)C.C(OCC)(=O)C.O>[C:5]([O:9][C:10]([N:11]1[C@@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[CH2:13][O:14][S:1]1(=[O:2])=[O:30])=[O:22])([CH3:8])([CH3:6])[CH3:7]

Participants

8

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 23667635Sodium periodateHCID 66763747Tert-butyl (S)-(1-(3-fluorophenyl)-2-hydroxyethyl)carbamate

Product 1

HCID 125497801HCID 125497801, compoundYield 86.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of thionyl chloride (1.64 mL, 22.5 mmol) in acetonitrile (40 mL) at −40° C. was added dropwise a solution of the [(S)-1-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (2.30 g, 9.0 mmol) in acetonitrile (100 mL) via addition funnel. Pyridine (3.64 mL, 45.0 mmol) was then added dropwise and the reaction was warmed to room temperature for 2 hours. The reaction was then concentrated to ¼ volume in vacuo and 350-400 mL of ethyl acetate was added. The resulting suspension was then filtered through Celite and the solids were washed with additional ethyl acetate. The filtrate was then concentrated to a sticky solid and dried under high vacuum briefly. The resulting residue was dissolved in acetonitrile (25 mL) and RuCl3—H2O (219 mg, 0.9 mmol) was added followed by sodium periodate (2.31 g, 10.8 mmol) and water (25 mL). The dark solution was stirred for 4 hours at which time it was diluted with ethyl acetate (100 mL) and water (100 mL) and the mixture was extracted with ethyl acetate three times. The combined organics were dried over sodium sulfate and concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane) to provide the product as a white solid (2.47 g, 86.4%).

Workup

  1. additionvia addition funnel
  2. concentrationThe reaction was then concentrated
  3. additionwas added
  4. filtrationThe resulting suspension was then filtered through Celite
  5. washthe solids were washed with additional ethyl acetate
  6. concentrationThe filtrate was then concentrated to a sticky solid
  7. customdried under high vacuum briefly
  8. dissolutionThe resulting residue was dissolved in acetonitrile (25 mL)
  9. extractionthe mixture was extracted with ethyl acetate three times
  10. dry with materialThe combined organics were dried over sodium sulfate
  11. concentrationconcentrated to a residue that
  12. customwas purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-d56e8cb265494f018271a608bc9c1d45
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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