Methanesulfonic Acid → (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-2-(2-(trifluoromethoxy)ethoxy)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

HRID 1175326Notes

Reaction equation

HRID 1175326 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH3:16])=[CH:11][CH:10]=2)[C:5]([Cl:17])=[CH:4][C:3]=1[O:18][CH2:19][CH2:20][O:21][C:22]([F:25])([F:24])[F:23].C[Si](C)(C)[O:28][C@@H:29]1[C@@H:34]([O:35][Si](C)(C)C)[C@H:33]([O:40][Si](C)(C)C)[C@@H:32]([CH2:45][O:46][Si](C)(C)C)[O:31][C:30]1=O.[Li]CCCC.CS(O)(=O)=O.[SiH](CC)(CC)CC.B(F)(F)F.CCOCC>C1COCC1.C(Cl)Cl>[Cl:17][C:5]1[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH3:16])=[CH:11][CH:10]=2)=[CH:7][C:2]([C@H:30]2[C@H:29]([OH:28])[C@@H:34]([OH:35])[C@H:33]([OH:40])[C@@H:32]([CH2:45][OH:46])[O:31]2)=[C:3]([O:18][CH2:19][CH2:20][O:21][C:22]([F:25])([F:24])[F:23])[CH:4]=1

Participants

9

Reactant 6

HCID 6395Methanesulfonic AcidHCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 59557719HCID 59557719, compoundHCID 178418339Butyllithium

Product 1

HCID 25169376(2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-2-(2-(trifluoromethoxy)ethoxy)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-bromo-4-chloro-5-(4-ethylbenzyl)-2-(2-(trifluoromethoxy)-ethoxy)benzene (BP) (60 mg, 0.14 mmol) and (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)-tetrahydropyran-2-one (0.19 g, 0.41 mmol) in anhydrous THF (2 mL), was added n-BuLi (2.5 M, 0.11 mL) in a dropwise fashion at −78° C. over 15 min. The resulting solution was stirred at −78° C. for 1 h. Methanesulfonic acid (20 μL in 0.5 mL MeOH) was added and the mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between EtOAc and saturated NaHCO3. The organic layer was dried with anhydrous Na2SO4, filtered and concentrated. The residue was purified by preparative TLC eluting with 5% MeOH in CH2Cl, to collect the crude product. To a solution of the crude product (10 mg, 0.018 mmol) in anhydrous CH2Cl2 (2 mL) at 0° C. was added Et3SiH (6.3 mg, 0.05 mmol) and BF3.Et2O (3.7 mg, 0.05 mmol). After stirring the resulting mixture for 1 h at 0° C., it was partitioned between water and EtOAc. The organic layer was dried over Na2SO4 and evaporated under vacuum. The residue was purified by preparative HPLC to give compound BQ. 1H-NMR (CDCl3, 300 MHz) δ 7.21 (s, 1H), 7.07 (m, 4H), 6.89 (s, 1H), 4.29 (d, J=3.9 Hz, 1H), 4.17 (m, 2H), 4.01 (m, 2H), 3.81 (m, 2H), 3.76 (m, 1H), 3.74-3.49 (m, 6H), 2.61 (m, 3H), 1.20 (m, 3H).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. customThe reaction mixture was partitioned between EtOAc and saturated NaHCO3
  4. dry with materialThe organic layer was dried with anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative TLC
  8. washeluting with 5% MeOH in CH2Cl
  9. customto collect the crude product
  10. stirringAfter stirring the resulting mixture for 1 h at 0° C.
  11. customit was partitioned between water and EtOAc
  12. dry with materialThe organic layer was dried over Na2SO4
  13. customevaporated under vacuum
  14. customThe residue was purified by preparative HPLC
  15. customto give compound BQ

Sources & evidence

ORD record
ord-efcb1bce686145eab74e9a87cf7db4e7
Source dataset
uspto-grants-2010_11
Patent number
US07838498B2

Reaction notes

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