Methanesulfonic Acid → HCID 68015102, compound

HRID 1913002Notes

Reaction equation

HRID 1913002 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:20])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[C:11]([F:18])[C:10]=2[F:19])[CH:7]=1.[Li][CH2:22]CCC.CCCCCC.C[Si](C)(C)[O:34][C@@H:35]1[C@@H:40]([O:41][Si](C)(C)C)[C@H:39]([O:46][Si](C)(C)C)[C@@H:38]([CH2:51][O:52][Si](C)(C)C)[O:37][C:36]1=[O:57].CS(O)(=O)=O>C1COCC1.CO>[Cl:20][C:5]1[CH:4]=[CH:3][C:2]([C@@:36]2([O:57][CH3:22])[C@H:35]([OH:34])[C@@H:40]([OH:41])[C@H:39]([OH:46])[C@@H:38]([CH2:51][OH:52])[O:37]2)=[CH:7][C:6]=1[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[C:11]([F:18])[C:10]=1[F:19]

Participants

8

Reactant 5

HCID 6395Methanesulfonic AcidHCID 8058HexaneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 86685118HCID 86685118, compoundHCID 178418339Butyllithium

Product 1

HCID 68015102HCID 68015102, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

1-[(5-bromo-2-chloro-phenyl)methyl]-4-ethoxy-2,3-difluoro-benzene 3e (5.5 g, 15.3 mmol) was dissolved in 20 mL THF and cooled to −78° C., followed by dropwise addition of a solution of n-BuLi in n-hexane (7.3 mL, 18.3 mmol). The reaction mixture was stirred for 1 hour at −78° C. 30 mL solution of (3R,4S,5R,6R)-3,4,5-tris (trimethylsilyloxy)-6-(trimethylsilyloxymethyl)tetrahydropyran-2-one 2f (7.5 g, 16.1 mmol) in THF at −78° C. were added before the reaction mixture was stirred for 2 hours at −78° C. A solution (51 mL) of 0.6 M methanesulfonic acid in methanol was added before the reaction mixture was warmed and stirred for 16 hours at room temperature. Thereafter, the reaction mixture was concentrated under reduced pressure, dissolved in water (50 mL) and extracted with ethyl acetate (100 mL×4). The organic extract was combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography with elution system A to obtain the title compound (2S,3R,4S,5S,6R)-2-[4-chloro-3-[(4-ethoxy-2,3-difluoro-phenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 3f (3.05 g, white solid), yield: 45.5%.

Workup

  1. stirringwas stirred for 2 hours at −78° C
  2. temperaturewas warmed
  3. stirringstirred for 16 hours at room temperature
  4. concentrationThereafter, the reaction mixture was concentrated under reduced pressure
  5. dissolutiondissolved in water (50 mL)
  6. extractionextracted with ethyl acetate (100 mL×4)
  7. extractionThe organic extract
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe resulting residue was purified by silica gel chromatography with elution system

Sources & evidence

ORD record
ord-975e0ebeae7646cd9a29d55a94e2863f
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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