Methanesulfonic Acid → HCID 57684696, compound

HRID 2038493Notes

Reaction equation

HRID 2038493 reaction equation
[CH2:1]([O:4][CH2:5][CH2:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][C:12]2[CH:17]=[C:16](Br)[CH:15]=[CH:14][C:13]=2[Cl:19])=[CH:9][CH:8]=1)[CH:2]=[CH2:3].[CH2:22]([O:29][C@@H:30]1[C@@H:35]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@H:34]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:33]([CH2:52][O:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[O:32][C:31]1=[O:61])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[CH2:62]([Li])CCC.CS(O)(=O)=O.C(=O)(O)[O-].[Na+]>C1COCC1.CCCCCC.CO.O>[CH2:1]([O:4][CH2:5][CH2:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][C:12]2[CH:17]=[C:16]([C@@:31]3([O:61][CH3:62])[C@H:30]([O:29][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C@@H:35]([O:36][CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C@H:34]([O:44][CH2:45][C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)[C@@H:33]([CH2:52][O:53][CH2:54][C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=4)[O:32]3)[CH:15]=[CH:14][C:13]=2[Cl:19])=[CH:9][CH:8]=1)[CH:2]=[CH2:3]

Participants

10

Reactant 5

HCID 6395Methanesulfonic AcidHCID 516892Sodium BicarbonateHCID 10907626(3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-((benzyloxy)methyl)oxan-2-oneHCID 59557775HCID 59557775, compoundHCID 178418339Butyllithium

Product 1

HCID 57684696HCID 57684696, compoundYield 28%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 2-(4-(2-(allyloxy)ethyl)benzyl)-4-bromo-1-chlorobenzene (intermediate BI) (123 mg, 0.34 mmol) and (3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-one (362 mg, 0.67 mmol) in anhydrous THF (1.5 mL) under argon and kept at −78° C. was added dropwise a 1.6 M solution of n-butyl lithium in hexane (0.63 mL) over 15 min. The mixture was stirred at −78° C. for 1.5 h. A solution of methanesulfonic acid (0.1 mL) in methanol (1 mL) was added to the reaction mixture and allowed to warm to room temperature over time. The mixture was stirred at room temperature for 21 h. A saturated solution of sodium bicarbonate was slowly added to the reaction mixture to bring the pH to 8. Water (2 mL) was added and the product was extracted into ethyl acetate (3×2 mL), the combined ethyl acetate solution was washed with brine (1.5 mL), dried (Na2SO4), filtered and evaporated. Preparative thin layer chromatography (TLC) using 12:1 hexane:EtOAc gave intermediate BJ (80 mg, yield 28%). LC-ESI-MS (m/z): 807 (M-OMe).

Workup

  1. customkept at −78° C.
  2. temperatureto warm to room temperature over time
  3. stirringThe mixture was stirred at room temperature for 21 h
  4. extractionthe product was extracted into ethyl acetate (3×2 mL)
  5. washthe combined ethyl acetate solution was washed with brine (1.5 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customEtOAc gave intermediate BJ (80 mg, yield 28%)

Sources & evidence

ORD record
ord-cbb5f21476a446d4b9e640924a75ab44
Source dataset
uspto-grants-2013_11
Patent number
US08575321B2

Reaction notes

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