Methanesulfonic Acid → (3R,4S,5S,6R)-2-(3-(4-((tert-butyldimethylsilyl)oxy)benzyl)-4-chlorophenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

HRID 628757Notes

Reaction equation

HRID 628757 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:20](I)=[CH:19][C:3]=1[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:7][CH:6]=1.[CH2:24]([Li])CCC.CCCCCC.C[Si](C)(C)[O:37][C@@H:38]1[C@@H:43]([O:44][Si](C)(C)C)[C@H:42]([O:49][Si](C)(C)C)[C@@H:41]([CH2:54][O:55][Si](C)(C)C)[O:40][C:39]1=[O:60].CS(O)(=O)=O>O1CCCC1.C1(C)C=CC=CC=1.CO>[Si:12]([O:11][C:8]1[CH:9]=[CH:10][C:5]([CH2:4][C:3]2[CH:19]=[C:20]([C:39]3([O:60][CH3:24])[C@H:38]([OH:37])[C@@H:43]([OH:44])[C@H:42]([OH:49])[C@@H:41]([CH2:54][OH:55])[O:40]3)[CH:21]=[CH:22][C:2]=2[Cl:1])=[CH:6][CH:7]=1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

9

Reactant 5

HCID 6395Methanesulfonic AcidHCID 8058HexaneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 1238887024-Iodo-1-chloro-2-[[4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]benzeneHCID 178418339Butyllithium

Product 1

HCID 123784895(3R,4S,5S,6R)-2-(3-(4-((tert-butyldimethylsilyl)oxy)benzyl)-4-chlorophenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

A solution of (4-(2-chloro-5-iodobenzyl)phenyloxy)tert-butyldimethylsilane (10.0 g, 21.8 mmol) in anhydrous tetrahydrofuran (80 mL) and toluene (80 mL) was cooled to −78° C. To the solution was slowly added dropwise a solution of n-butyl lithium in n-hexane (2.4 mol/L, 13.6 mL, 32.6 mmol). The resulting mixture was reacted at −78° C. for 2 hr, and then warmed up to −60° C. To the reaction mixture was added a solution of (3R,4S,5R,6R)-3,4,5-tri((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetra hydro-2H-pyran-2-one (15.3 g, 32.7 mmol) in toluene (60 mL) in one batch. The resulting mixture was reacted at −60° C. for 2 hr. To the reaction mixture was added dropwise a solution of methanesulfonic acid (14.6 g, 152.1 mmol) in methanol (50 mL). After the completion of dropwise addition, the resulting mixture was reacted under stirring at room temperature for 17 hr. The reaction mixture was quenched with a saturated sodium bicarbonate solution, and separated into an aqueous phase and an organic phase. The aqueous phase was extracted with ethyl acetate (200 mL×3). The organic phases were combined, washed with a saturated sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under a reduced pressure to produce 9.0 g of a crude product, which was directly used in the next reaction without purification.

Workup

  1. customThe resulting mixture was reacted at −78° C. for 2 hr
  2. customThe resulting mixture was reacted at −60° C. for 2 hr
  3. additionAfter the completion of dropwise addition
  4. customthe resulting mixture was reacted
  5. customThe reaction mixture was quenched with a saturated sodium bicarbonate solution
  6. customseparated into an aqueous phase
  7. extractionThe aqueous phase was extracted with ethyl acetate (200 mL×3)
  8. washwashed with a saturated sodium chloride solution
  9. dry with materialdried over anhydrous sodium sulphate
  10. concentrationconcentrated under a reduced pressure

Sources & evidence

ORD record
ord-837d3f798add4578a823c9e297008dae
Source dataset
uspto-grants-2016_04
Patent number
US09315438B2

Reaction notes

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