Hydrochloric Acid → Methyl 1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-alpha-D-glucopyranoside

HRID 1470054Notes

Reaction equation

HRID 1470054 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH:3]=1.[Li][CH2:20]CCC.C[Si](C)(C)[O:26][C@@H:27]1[C@@H:32]([O:33][Si](C)(C)C)[C@H:31]([O:38][Si](C)(C)C)[C@@H:30]([CH2:43][O:44][Si](C)(C)C)[O:29][C:28]1=[O:49].Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1(C)C=CC=CC=1.CO>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C@@:28]2([O:49][CH3:20])[C@H:27]([OH:26])[C@@H:32]([OH:33])[C@H:31]([OH:38])[C@@H:30]([CH2:43][OH:44])[O:29]2)=[CH:3][C:4]=1[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 178418339Butyllithium

Product 1

HCID 24807437Methyl 1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-alpha-D-glucopyranoside

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-65 °C

Procedure

To a solution of Example 1B (200 g, 0.614 mol) in anhydrous toluene/THF (1.2 L, 2:1 (v/v)) was added n-BuLi (2.5 M in hexane, 295 mL) dropwise at −65° C. The reaction was stirred at −65° C. for 30 min. Then the mixture was transferred by a cannula to a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one) (373 g, 0.798 mol) in toluene (1.2 L) at −65° C. The mixture was stirred at −65° C. until starting material was consumed (2 h). The reaction was quenched with hydrochloric acid (36˜38%, 113 mL, 1.35 mol) in methanol (800 mL), and stirred at room temperature overnight. The reaction was neutralized with saturated sodium bicarbonate to pH 7.5 and the organic phase was separated and the aqueous phase was extracted with ethyl acetate (2×3.0 L). The combined organic layers were washed with brine (2×2.0 L), dried over sodium sulfate and concentrated. The residue was dissolved in hot toluene (600 mL) and poured into n-hexane (2.0 L) with vigorous stirring. After stirring for 1 h, the mixture was filtered and the filter cake was dried under vacuum to give the desired product as a white solid. This solid was used without further purification in the next step. MS ESI (m/z) 439 [M+1]+.

Workup

  1. customat −65° C
  2. stirringThe mixture was stirred at −65° C.
  3. customwas consumed (2 h)
  4. stirringstirred at room temperature overnight
  5. customthe organic phase was separated
  6. extractionthe aqueous phase was extracted with ethyl acetate (2×3.0 L)
  7. washThe combined organic layers were washed with brine (2×2.0 L)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in hot toluene (600 mL)
  11. additionpoured into n-hexane (2.0 L) with vigorous stirring
  12. stirringAfter stirring for 1 h
  13. filtrationthe mixture was filtered
  14. customthe filter cake was dried under vacuum

Sources & evidence

ORD record
ord-e789103d11544b41bdc0144f204e3ec9
Source dataset
uspto-grants-2015_04
Patent number
US09006403B2

Reaction notes

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