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

HRID 1175297Notes

Reaction equation

HRID 1175297 reaction equation
[CH2:1]([O:4][CH2:5][C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH3:21])=[CH:16][CH:15]=2)=[CH:8][C:7]=1Br)[CH:2]=[CH2:3].[Li][CH2:24]CCC.C[Si](C)(C)[O:30][C@@H:31]1[C@@H:36]([O:37][Si](C)(C)C)[C@H:35]([O:42][Si](C)(C)C)[C@@H:34]([CH2:47][O:48][Si](C)(C)C)[O:33][C:32]1=[O:53].CS(O)(=O)=O>C1COCC1.C1(C)C=CC=CC=1.C1(C)C=CC=CC=1.CO>[CH2:1]([O:4][CH2:5][C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH3:21])=[CH:16][CH:15]=2)=[CH:8][C:7]=1[C@@:32]1([O:53][CH3:24])[C@H:31]([OH:30])[C@@H:36]([OH:37])[C@H:35]([OH:42])[C@@H:34]([CH2:47][OH:48])[O:33]1)[CH:2]=[CH2:3]

Participants

8

Reactant 4

HCID 6395Methanesulfonic AcidHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 595576981-(Allyloxymethyl)-2-bromo-5-chloro-4-(4-ethylbenzyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 59557701(2S,3R,4S,5S,6R)-2-(2-(allyloxymethyl)-4-chloro-5-(4-ethylbenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 1140TolueneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

To a solution of 1-(allyloxymethyl)-2-bromo-5-chloro-4-(4-ethylbenzyl)benzene in dry THF:toluene (1:2, 2.4 mL) was added n-BuLi (0.3 mL, 2.5 M in hexane) dropwise under argon. After it was stirred for 1 h, a cooled solution (−70° C.) of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)-tetrahydropyran-2-one in dry toluene (1.8 mL) was added dropwise to the reaction mixture. After being stirred for 3 h, the reaction was quenched by addition of ice water and extracted with EtOAc. The combined organic layers were washed 2× with water, 2× with brine, and then dried over Na2SO4. Concentration gave a yellow oil, which was dissolved in 20 mL of methanol, and methanesulfonic acid in 5 mL of methanol was added. The reaction mixture was stirred over 50 h under argon prior to being quenched by addition of satd NaHCO3 to pH 7.5. Concentration gave a residue, which was purified by preparative TLC to yield 14 mg of title compound as a white solid. 1H-NMR (CD3OD, 400 MHz) δ 7.48 (s, 1H), 7.36 (s, 1H), 7.03 (s, 4H), 5.93-5.87 (m, 1H), 5.24 (dd, J=17.2 Hz, 1.6 Hz, 1H), 5.11 (dd, J=1.6 Hz, 10.4 Hz, 1H), 4.70 (m, 3H), 4.06-3.89 (m, 4H), 3.82 (dd, J=2.4 Hz, 12.4 Hz, 1H), 3.71-3.62 (m, 2H), 3.50-3.46 (m, 1H), 3.26-3.22 (m, 1H), 3.00 (s, 3H), 2.78-2.74 (m, 1H), 1.12 (d, J=7.2 Hz, 6H); LC-MS (m/z) 493 [(M+1)+].

Workup

  1. stirringAfter being stirred for 3 h
  2. customthe reaction was quenched by addition of ice water
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed 2× with water, 2× with brine
  5. dry with materialdried over Na2SO4
  6. concentrationConcentration
  7. customgave a yellow oil, which
  8. stirringThe reaction mixture was stirred over 50 h under argon
  9. customto being quenched by addition of satd NaHCO3 to pH 7.5
  10. concentrationConcentration
  11. customgave a residue, which
  12. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-81d3e93398ab4ddcba9f3ae4de95909b
Source dataset
uspto-grants-2010_11
Patent number
US07838498B2

Reaction notes

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