Methanesulfonic Acid → (3R,4S,5S,6R)-2-(2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

HRID 1175324Notes

Reaction equation

HRID 1175324 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=2)[C:5]([Cl:18])=[CH:4][C:3]=1[CH2:19][CH2:20][CH2:21][O:22][CH2:23][C:24]#[C:25][CH3:26].[Li][CH2:28]CCC.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.CCCCCC.C1(C)C=CC=CC=1.CO>[CH2:23]([O:22][CH2:21][CH2:20][CH2:19][C:3]1[CH:4]=[C:5]([Cl:18])[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=2)=[CH:7][C:2]=1[C:36]1([O:57][CH3:28])[C@H:35]([OH:34])[C@@H:40]([OH:41])[C@H:39]([OH:46])[C@@H:38]([CH2:51][OH:52])[O:37]1)[C:24]#[C:25][CH3:26]

Participants

9

Reactant 4

HCID 6395Methanesulfonic AcidHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 59557729HCID 59557729, compoundHCID 178418339Butyllithium

Product 1

HCID 59557682(3R,4S,5S,6R)-2-(2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a stirred −78° C. solution of 1-bromo-2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)benzene (BM) (0.2 g, 0.459 mmol) in 3 mL of 1:2 dry THF:toluene under Ar was added 0.22 mL of 2.5M n-BuLi in hexane (precooled to −78° C.) dropwise to insure the temperature remained below −70° C. After stirring for 40 min, the solution was transferred by cannula to a stirred −78° C. solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)-tetrahydropyran-2-one (0.279 g, 0.597 mmol) in 2.5 mL of toluene at a rate that maintained the reaction below −70° C. The mixture was stirred for 3 h at −78° C. prior to addition of MeSO3H (0.093 g, 0.964 mmol) in 2.5 mL of methanol below −75° C. After complete addition, the reaction solution was gradually warmed to room temperature and stirred overnight. After quenching by saturated aq. NaHCO3, the aqueous layer was extracted twice with EtOAc. The combined organic portions were washed with brine and dried over Na2SO4. After concentration, the residue was purified by preparative TLC (eluting with EtOAc:PE=1:5) to obtain 0.11 g of intermediate BN.

Workup

  1. customremained below −70° C
  2. customwas transferred by cannula to a stirred −78° C.
  3. temperaturemaintained
  4. customthe reaction below −70° C
  5. stirringThe mixture was stirred for 3 h at −78° C.
  6. additionAfter complete addition
  7. stirringstirred overnight
  8. customAfter quenching by saturated aq. NaHCO3
  9. extractionthe aqueous layer was extracted twice with EtOAc
  10. washThe combined organic portions were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationAfter concentration
  13. customthe residue was purified by preparative TLC (eluting with EtOAc:PE=1:5)

Sources & evidence

ORD record
ord-4823d03c13d84fc2b5cef61386c274de
Source dataset
uspto-grants-2010_11
Patent number
US07838498B2

Reaction notes

Loading…