Methanesulfonic Acid → HCID 68015194, compound

HRID 1913014Notes

Reaction equation

HRID 1913014 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:19])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[C:11]([F:18])[CH:10]=2)[CH:7]=1.[Li][CH2:21]CCC.CCCCCC.C[Si](C)(C)[O:33][C@@H:34]1[C@@H:39]([O:40][Si](C)(C)C)[C@H:38]([O:45][Si](C)(C)C)[C@@H:37]([CH2:50][O:51][Si](C)(C)C)[O:36][C:35]1=[O:56].CS(O)(=O)=O>C1COCC1.CO>[Cl:19][C:5]1[CH:4]=[CH:3][C:2]([C@@:35]2([O:56][CH3:21])[C@H:34]([OH:33])[C@@H:39]([OH:40])[C@H:38]([OH:45])[C@@H:37]([CH2:50][OH:51])[O:36]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])[CH:10]=1

Participants

8

Reactant 5

HCID 6395Methanesulfonic AcidHCID 8058HexaneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 67069134HCID 67069134, compoundHCID 178418339Butyllithium

Product 1

HCID 68015194HCID 68015194, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

4-[(5-bromo-2-chloro-phenyl)methyl]-1-ethoxy-2-fluoro-benzene 4e (7.36 g, 21.4 mmol) was dissolved in 30 mL THF and cooled to −78° C., followed by dropwise addition of a solution of nBuLi in n-hexane (10.27 mL, 25.7 mmol). After stirring for 1 hour at −78° C., a solution (20 mL) of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-(trimethylsilyloxymethyl)tetrahydropyran-2-one 2f (11 g, 23.6 mmol) in THF was added before the reaction mixture was stirred for 2 hours at −78° C. Then the reaction mixture was warmed and stirred for 16 hours at room temperature after 2.8 mL methylsulfonic acid and 71 mL methanol were added. Thereafter, the reaction mixture was concentrated under reduced pressure after 100 mL saturated sodium carbonate solution were added. The residue was dissolved in 50 mL saturated sodium chloride, extracted with ethyl acetate (100 mL×3). The organic extract was combined, dried over anhydrous magnesium sulfate, 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-3-fluoro-phenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 4f (5.7 g, white solid), yield: 58.3%. 1H NMR (400 MHz, CD3OD): δ 7.56 (s, 1H), 7.48 (dd, 1H), 7.37 (dd, 1H), 6.95-6.87 (m, 3H), 4.08-4.07 (m, 4H), 3.91 (m, 1H), 3.93-3.73 (m, 2H), 3.56-3.53 (m, 1H), 3.45-3.43 (m, 1H), 3.30 (s, 2H), 3.08 (s, 3H), 1.35 (t, 3H).

Workup

  1. stirringwas stirred for 2 hours at −78° C
  2. temperatureThen the reaction mixture was warmed
  3. additionwere added
  4. concentrationThereafter, the reaction mixture was concentrated under reduced pressure after 100 mL saturated sodium carbonate solution
  5. additionwere added
  6. dissolutionThe residue was dissolved in 50 mL saturated sodium chloride
  7. extractionextracted with ethyl acetate (100 mL×3)
  8. extractionThe organic extract
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customthe resulting residue was purified by silica gel chromatography with elution system

Sources & evidence

ORD record
ord-91f4541a9c274017b1c4bebb73a32c93
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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